Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 101: 740-744, 2006. First published May 25, 2006; doi:10.1152/japplphysiol.00144.2006
8750-7587/06 $8.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
101/3/740    most recent
00144.2006v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (7)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, J.-S.
Right arrow Articles by Chow, S.-E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, J.-S.
Right arrow Articles by Chow, S.-E.

Role of exercise intensities in oxidized low-density lipoprotein-mediated redox status of monocyte in men

Jong-Shyan Wang,1 Tan Lee,2 and Shu-Er Chow3

1Institution of Coaching Science, National College of Physical Education & Sports, Tao-Yuan; 2Department of Physiology, and 3Graduate Institute of Rehabilitation Science and Center for Gerontological Research, Chang Gung University, Tao-Yuan, Taiwan

Submitted 5 February 2006 ; accepted in final form 9 May 2006


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Exercise significantly influences the progression of atherosclerosis. Oxidized LDL (ox-LDL), as a stimulator of oxidative stress, facilitates monocyte-related atherogenesis. This study investigates how exercise intensity impacts ox-LDL-mediated redox status of monocytes. Twenty-five sedentary healthy men exercised mildly, moderately, and heavily (i.e., 40, 60, and 80% maximal oxygen consumption, respectively) on a bicycle ergometer. Reactive oxygen species (ROS) production, cytosolic and mitochondrial superoxide dismutase (c-SOD and m-SOD, respectively) activities, and total and reduced-form {gamma}-glutamylcysteinyl glycine (t-GSH and r-GSH, respectively) contents in monocytes mediated by ox-LDL were measured. This experiment obtained the following findings: 1) ox-LDL increased monocyte ROS production and was accompanied by decreased c-SOD and m-SOD activities, as well as t-GSH and r-GSH contents, whereas treating monocytes with diphenyleneiodonium (DPI) (a NADPH oxidase inhibitor) or rotenone/2-thenoyltrifluoroacetone (TTFA) (mitochondrial complex I/II inhibitors) hindered ox-LDL-induced monocyte ROS production; 2) production of ROS and reduction of m-SOD activity and r-GSH content in monocyte by ox-LDL were enhanced by heavy exercise and depressed by mild and moderate exercise; and 3) heavy exercise augmented the inhibition of ox-LDL-induced monocyte ROS production by DPI and rotenone/TTFA, whereas these DPI- and rotenone/TTFA-mediated monocyte ROS productions were unchanged in response to mild and moderate exercise. We conclude that heavy exercise increases ox-LDL-induced monocyte ROS production, possibly by decreasing m-SOD activity and r-GSH content in monocytes. However, mild and moderate exercise likely protects individuals against suppression of anti-oxidative capacity of monocyte by ox-LDL.

physical activity; reactive oxygen species; SOD, GSH

ALTHOUGH REGULAR MODERATE-INTENSITY EXERCISE decreases the risk of cardiovascular disease (10, 20), episodes of vigorous exertion transiently increase the occurrence of sudden cardiac arrest (1, 18). Atherosclerosis, a chronic inflammatory disease of the vessel wall, is characterized by archetypical chronic inflammatory cell infiltration of monocytes (5, 6, 11). Experimental evidence indicates that reactive oxygen species (ROS) derived from infiltrated monocytes contribute to oxidative stress at inflammatory sites, thereby promoting oxidation of low-density lipoprotein (LDL) (3). Moreover, oxidized LDL (ox-LDL) has been identified as a potent chemoattractant and oxidative stressor of atherogenesis, typically causing endothelium dysfunction and facilitating monocyte emigration into the subendothelial space (11). Therefore, elucidating the regulation of ox-LDL-induced ROS production in monocytes can lead to a novel therapeutic intervention for prevention of atherosclerosis.

Physical exercise modulates inflammatory reactions in leukocytes, according to reactions based on the exercise type/intensity/duration (16). Previous studies (7, 21) indicated that strenuous exercise generates an imbalance between ROS and antioxidant defense, resulting in an oxidative stressful environment in the body. Conversely, regular moderate-intensity exercise hinders LDL oxidation by enhancing antioxidant release or production (24). Whether physical exercise influences oxidant production and antioxidative capacity of monocyte mediated by ox-LDL remains unclear. We hypothesize that exercise impacts ox-LDL-mediated redox status of monocytes, with reactions determined by exercise intensity.

This study clarifies how exercise intensity affects ox-LDL-mediated ROS production and antioxidative capacity in monocytes. Furthermore, activating membrane-associated NADPH oxidase (2) and changing the coupling of the mitochondrial respiratory chain (15) are the critical pathways in monocyte ROS-mediated atherogenesis noted in previous studies. Therefore, this study also determined whether exercise affects ox-LDL-induced monocyte ROS production through altering the signal transductions in these pathways.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Subjects.   The Ethics Committee of Chang Gung Memorial Hospital reviewed and approved the protocol for this study. Procedures corresponded to institutional guidelines. All subjects provided informed, written consent. Twenty-five healthy sedentary men were enrolled in this study. Subject characteristics (expressed as means ± SE) were as follows: age, 23.7 ± 0.4 yr; height, 171.5 ± 1.1 cm; and body weight, 67.3 ± 1.4 kg (Table 1). No subject had engaged in regular physical activity for at least 1 yr before study start. All subjects were infection free or cardiovascular risk free and abstained from all medication and vitamins at least for 2 wk before the study. Subjects fasted for at least 8 h before study participation and were instructed to refrain from exercise for at least 24 h before blood sampling. All subjects arrived at the test center at 9:00 AM to eliminate possible diurnal influence.


View this table:
[in this window]
[in a new window]
  		Table 1. Anthropometric characteristics and exercise performance in all subjects

 
Exercise and blood collection protocol.   The subjects came to the laboratory on 4 different days to receive four distinct exercise protocols on a bicycle ergometer (Lode, Corival 400) (Table 1). The first protocol comprised 2 min of unloaded pedaling, after which workload was increased incrementally by 20–30 W every 3 min until subjects were exhausted. Heart rate, minute ventilation, oxygen consumption, and carbon dioxide production were measured during the exercise with an automated system (PowerLab/8M; AD Instruments). This exercise test determined each subject's maximal oxygen consumption (VO2 max) (25). The VO2 max was defined as the following four criteria: 1) the increase of oxygen consumption was <2 ml·kg–1·min–1 in the last 2 min of exercise; 2) heart rate arrived at its predicted maximum; 3) the respiratory exchange ratio exceeded 1.20; and 4) venous lactate concentration after the termination of exercise exceeded 8 mM. The value of subjects' VO2 max was 35.9 ± 1.4 ml·kg–1·min–1 (mean ± SE). In the second, third, and fourth exercise protocols, subjects performed at ~40% (mild), 60% (moderate), and 80% (heavy) of predetermined VO2 max for 40 min (Table 1). According to the values of heart rate and oxygen consumption during exercise, the workload of bicycle ergometer was adjusted in real time to confirm that the subjects truly exercised at the prescribed exercise intensities. The second to fourth exercise protocols were randomized in a counterbalanced order. Each test was separated by 2 wk to ensure complete recovery between trials. If a subject was ill or had a fever, the test was postponed until the subject was symptom free and medication free for least 2 wk. At rest and immediately after mild, moderate, or heavy exercise, blood samples, collected from a forearm vein, were used to measure hematological parameters and monocyte function. Blood cell counts were analyzed using a Sysmex KX-21 cell counter.

ox-LDL preparation in human.   ox-LDL was prepared from fresh human plasma, as described previously (26). Thiobarbituric acid reactive substances was estimated colorimetrically by using malondialdehyde as a standard; starting LDL was 0.06 nmol of malondialdehyde/mg protein, and ox-LDL was 13.80 nmol of malondialdehyde/mg protein.

Monocyte separation.   Thirty milliliters of blood sample at rest and immediately after exercise was transferred into polypropylene tubes containing sodium citrate. Peripheral blood monocytes were isolated by Dynabead M-450 CD14 (Dynal ASA) using an immunomagnetic selection technique, as described previously (19). Monocytes were resuspended in Hanks' solution with 2 mM CaCl2, pH 7.4, and adjusted to 2x105 cells/ml. Analysis of monocyte function was completed within 2 h following cell purification.

Monocyte ROS production.   Monocytes (2x105 cells/ml) were incubated in 495 µl of Hanks' solution, pH 7.4, with 5 µl of dihydroethidium working solution (final concentration, 5 µM) (Sigma) in a polypropylene test tube for 20 min at 37°C. Following incubation, monocytes were washed and respuspended in Hank's solution, pH 7.4 (2x105 cells/ml) (Sigma). For certain experiments, various pharmacological reagents, such as 1, 5, and 10 µM diphenylene iodonium (DPI; a compound that binds to and inhibits flavin-containing oxidase) (Sigma), 10, 100, and 1,000 µM staurosporin A (an inhibitor for protein kinase C) (Sigma), and 1, 5, and 10 µM glibeclamide (a selective blocker of mitochondrial KATP channel) (Sigma), as well as 10 µM rotenone (Sigma), 2-thenoyltrifluoroacetone (TTFA; Sigma), and antimycin A (Sigma) (i.e., mitochondrial complex I, II, and III inhibitors, respectively) were added to the monocyte suspension, which was then warmed to 37°C for 10 min. Following incubation, these reagent-treated monocytes were washed and immediately added to a polypropylene test tube with and without ox-LDL (final concentration, 10 µg/ml) for 30 min at 37°C. The fluorescence obtained from 5,000 events that represented the monocyte, was determined using a flow cytometer, as described previously (23).

Monocyte SOD activities and GSH contents.   The monocyte suspensions (2x105 cells/ml) were incubated in the absence or presence of ox-LDL (final concentration, 10 µg/ml) for 30 min at 37°C. Then a mitrochondria/cytosol fractionation kit (Biovision) was applied to separate mitochodria from cytosols of monocytes. In brief, the monocyte suspensions (2x105 cells/ml) were incubated with cytosol extraction buffer mix (Biovision) at 4°C for 10 min and then centrifuged at 700 g for 10 min at 4°C. The suspension was recentrifuged at 10,000 g for 30 min at 4°C, and then the supernatant was collected cytosolic fraction. The pellet was resuspended with mitochondrial extraction buffer mix (Biovision), vortexed for 10 s, and saved as the mitochondrial fraction. Cytosolic and mitochondrial superoxide dismutase (c-SOD and m-SOD, respectively) activities in monocytes were calculated with a commercial SOD assay kit (Cayman). This SOD assay kit utilizes a tetrazolium salt for detecting superoxide radicals produced by xanthine oxidase and hypoxanthine. One unit of SOD is defined as the amount of enzyme needed to exhibit 50% dismutation of the superoxide radical. Additionally, total and reduced-form {gamma}-glutamylcysteinly glycine (t-GSH and r-GSH, respectively) contents in monocytes were measured with commercial GSH colorimeter detection kit (BioVision). This assay was based on the glutathione recycling system by 5,5-dithio-(2-nitrobenzoic acid) (DTNB) and glutathione reductase. DTNB and GSH reacted to generate 2-nitro-5-thiobenzoic acid and GSSG. Therefore, concentration of GSH was determined by measuring absorbance of 2-nitro-5-thiobenzoic acid at 412 nm. GSH was regenerated from GSSG by glutathione reductase and reacted with DTNB again to produce more 2-nitro-5-thiobenzoic acid. Thus total GSH concentration was obtained from this recycling system. This kit also specifically detected the reduced form of GSH by omitting the glutathione reductase from the reaction mixture.

Statistics.   Data are expressed as means ± SE. The StatView IV statistical software package was employed for data analysis. Monocyte counts, ROS production, SOD activity, and GSH content at rest and immediately after mild, moderate, and heavy exercise were compared using repeated-measure ANOVA and Tukey's multiple range test. Statistical significance was set at P < 0.05.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Leukocyte counts.   Heavy exercise significantly elevated levels of total leukocyte counts, including neutrophils, eosinphils, basophils, lymphocytes, and monocytes of its subgroups (data not shown) (P < 0.05). Although moderate exercise modestly increased neutrophil and lymphocyte counts (P < 0.05), no significant changes occurred for eosinphil, basophil, and monocyte counts. Additionally, no significant changes occurred for all leukocyte subgroups immediately after mild exercise (data not shown).

Monocyte ROS production.   ox-LDL induced a significant increase in ROS production of monocytes (Table 2). Heavy exercise further enhanced monocyte ROS production by ox-LDL compared with that for moderate and mild exercise (P < 0.05) (Table 2). Although enhancement of ox-LDL was suppressed by rotenone (30.5 ± 4.2%), TTFA (42.5 ± 5.6%), and rotenone plus TTFA (62.5 ± 3.5%), it remained unaltered in response to antimycin A (Fig. 1). Furthermore, incubation of monocytes in the presence of DPI, glibeclamide, or staurosporin A also caused a marked concentration-dependent suppression of ox-LDL-promoted ROS production of monocytes (P < 0.05) (Fig. 1). Inhibition of ox-LDL-induced monocyte ROS production by DPI and rotenone plus TTFA was enhanced by heavy exercise (P < 0.05) (Fig. 2) and was unchanged by moderate and mild exercise (Fig. 2).


View this table:
[in this window]
[in a new window]
  		Table 2. Effects of exercise intensities on ROS production in monocytes

 

Figure 1
View larger version (13K):
[in this window]
[in a new window]
  		Fig. 1. Effects of vehicle (Hanks' solution; A), mitochondrial complex I (rotenone), II (TTFA), and III (antimycin A) inhibitors (B), NADPH oxidase inhibitor (DPI; C), mitochondrial KATP channel blockor (glibeclamide; D), and protein kinase C inhibitor (SA; E) on oxidated LDL (ox-LDL)-induced reactive oxygen species (ROS) production of monocyte. *P < 0.05, vehicle vs. various pharmacological reagents.

 

Figure 2
View larger version (21K):
[in this window]
[in a new window]
  		Fig. 2. Effects of mild (A), moderate (B), and heavy exercise (C) on inhibitions of ox-LDL-induced monocyte ROS production by 10 µM rotenone/TTFA, 10 µM DPI, 10 µM glibeclamide, and 1,000 µM SA. R, at rest; E, immediately after exercise. *P < 0.05, R vs. E.

 
Monocyte SOD activity and GSH content.   ox-LDL suppressed c-SOD and m-SOD activities (P < 0.05) (Table 3) as well as r-GSH and t-GSH contents and r-GSH-to-t-GSH ratio (P < 0.05; Table 4) in monocytes. Heavy exercise reduced basal and ox-LDL-treated c-SOD and m-SOD activities, r-GSH and t-GSH contents, and r-GSH-to-t-GSH ratio in monocytes (P < 0.05) (Tables 3 and 4). Conversely, moderate and mild exercise did not yield these changes in basal c-SOD and m-SOD activities, t-GSH and r-GSH contents, and r-GSH-to-t-GSH ratio in monocytes, whereas the two exercise regimes prevented monocytes from diminishing c-SOD and m-SOD activity and t-GSH and r-GSH content by ox-LDL treatment (Tables 3 and 4). Additionally, no significant change was observed in plasma SOD activity, t-GSH and r-GSH content, and r-GSH-to-t-GSH ratio after mild, moderate, and heavy exercise (Tables 3 and 4).


View this table:
[in this window]
[in a new window]
  		Table 3. Effects of exercise intensities on SOD activities in plasma and monocytes

 

View this table:
[in this window]
[in a new window]
  		Table 4. Effects of exercise intensities on GSH contents in plasma and monocytes

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
This study is the first to clearly demonstrate that exercise intensity is an important factor impacting ox-LDL-mediated redox status in monocytes. 1) Heavy exercise enhances suppression of m-SOD activity and r-GSH content by ox-LDL, whereas both mild and moderate exercise reduce the effects of ox-LDL on m-SOD and r-GSH. 2) Although heavy exercise increases ox-LDL-induced ROS production from NADPH oxidase and mitochondria in monocyte, both moderate and mild exercise did not influence ox-LDL-induced monocyte ROS production.

Regulation of ROS production in monocytes contributes to the atherosclerotic process (2, 15). Increased ROS level by changed coupling of mitochondrial electron transport chain or activated mitochondrial KATP channel participate in abnormal vascular responses and subsequent progression of atherosclerosis (9, 12, 13). Additionally, leukocyte-derived ROS was also elevated by the enhancement of NADPH oxidase activity under vascular inflammatory conditions (29). Production of ROS induced by chemoattractants promoted expression of adhesion molecules (e.g., Mac-1) and strengthened adhesion by leukocytes, whereas suppression of ROS production by NADPH oxidase through interfering with PKC-dependent signals limited leukocyte adhesion to endothelium (29). Experimental results in this study showed that ox-LDL increased monocyte-derived ROS. However, treating monocytes with DPI, staurosporin A, rotenone/TTFA, or glibeclamide hindered ROS production induced by ox-LDL. Therefore, ox-LDL enhanced monocyte ROS production, likely by activating membrane-associated NADPH oxidase and changing the coupling of the mitochondrial respiratory chain. Heavy exercise further enhanced monocyte-derived ROS by ox-LDL and also increased the inhibition of ox-LDL-induced monocyte ROS production by DPI and rotenone/TTFA, suggesting that heavy exercise can increase ox-LDL-induced ROS production from both NADPH oxidase and mitochondria of monocytes. However, moderate and mild exercise did not influence the degree of monocyte-derived ROS enhanced by ox-LDL; the NADPH oxidase- and mitochondria-mediated ROS production of monocytes remained unchanged in response to moderate and mild exercise.

Numerous scavenging systems limit cellular ROS levels in leukocyte; i.e., superoxide is dismutated by a family of SODs (such as MnSOD in mitochodria and Cu/ZnSOD in cytoplasm) to H2O2, and then H2O2 is scavenged into water by glutathione peroxidase in the presence of r-GSH (8). ox-LDL suppresses antioxidative capacity in monocytes by decreasing c-SOD and m-SOD activities and r-GSH and t-GSH contents as well as r-GSH-to-t-GSH ratio in this study. Furthermore, heavy exercise decreased basal and ox-LDL-treated c-SOD and m-SOD activities, r-GSH and t-GSH contents, and r-GSH-to-t-GSH ratio in monocyte. Therefore, heavy exercise decreased levels or activities of these antioxidants in monocytes, possibly predisposing monocytes toward the pro-oxidative status, thereby enhancing ox-LDL-induced ROS production from cytoplasm and mitochondria of monocytes. Although moderate and mild exercise did not change basal c-SOD and m-SOD activities, t-GSH and r-GSH contents, and r-GSH-to-t-GSH ratio in monocytes, diminished SOD and GSH bioavailability by ox-LDL was retarded by the two exercise regimes. Therefore, increased antioxidative capacity of monocytes after mild- and moderate-intensity exercise lowers monocyte activation induced by oxidative stress, which, in turn, typically inhibits monocyte-related atherogenesis.

The amount of oxidative stress induced by physical exercise is determined by the level of free-radical generation and the defensive capacity of antioxidants (8). A previous study demonstrated that mitochondrial lipid peroxidation in skeletal muscle was enhanced after strenuous exercise, accompanied by a loss of protein thiol content (14). A recent investigation by the authors of this study also demonstrated that heavy exercise reduced lymphocyte GSH content and mitochondrial transmembrane potential (27). Their experimental findings were similar with some of the results obtained by this study that evaluated redox status of monocytes. Declining leukocyte GSH level following heavy exercise potentially may result in an accelerated cell efflux or a lowered rate of uptake of precursors and subsequent resynthesis (4, 22). A previous study showed that oxidative stress enhanced glutathione efflux of leukocytes through activating the plasma membrane enzyme {gamma}-glutamyl transpeptidase (4). When moncocytes are treated with ox-LDL, accelerated monocyte GSH depletion by heavy exercise leads to reduced antioxidative capacity of monocytes, subsequently promoting monocyte ROS production induced by ox-LDL. Conversely, a recent work displayed that moderate exercise elevated GSH content and decreased lipid peroxidation in lymphocytes, suppressing H2O2-induced oxidative damage of lymphocytes (27). Additionally, regular moderate exercise also suppresses ox-LDL-promoted platelet activation by enhancing nitric oxide release (as an antioxidant) of platelets (26). Moreover, this study also identified an inhibitive effect on diminished SOD activity and GSH content by ox-LDL following mild and moderate exercise. Therefore, mild- to moderate-intensity exercise can plausibly be considered safe and effective for minimizing atherosclerotic risk by promoting antioxidative capacity in monocytes or other atherogenetic-related cells such as platelets and lymphocytes.

In conclusion, ox-LDL-mediated redox status in monocytes is affected by acute exercise in an intensity-dependent manner (i.e., heavy exercise promotes ox-LDL-induced monocyte ROS production, likely by reducing m-SOD activity and r-GSH content in monocytes), whereas mild and moderate exercise attenuate suppression of monocyte antioxidative capacity by ox-LDL. These experimental findings can assist in determining suitable exercise regimes to prevent early atherosclerotic events and further hinder cardiovascular disease progression.


   GRANTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
ACKNOWLEDGMENTS
 REFERENCES
 
The study was supported under the National Science Council Grant of the Republic of China, Taiwan (NSC 94-2314-B-182-026).


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
REFERENCES
 
The authors thank the volunteers for enthusiastic participation in this study.


   FOOTNOTES
 

Address for reprint requests and other correspondence: J.-S. Wang, Graduate Institute of Rehabilitation Science, Chang Gung Univ., 259 Wen-Hwa 1st Rd., Kwei-Shan, Tao-Yuan, 333, Taiwan (e-mail: s5692{at}mail.cgu.edu.tw)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 

  1. Albert CM, Mittleman MA, Chae CU, Lee IM, Hennekens CH, and Manson JE. Triggering of sudden death from cardiac causes by vigorous exertion. N Engl J Med 343: 1355–1361, 2000.[Abstract/Free Full Text]
  2. Cathcart MK. Regulation of superoxide anion production by NADPH oxidase in monocytes/macrophages: contributions to atherosclerosis. Arterioscler Thromb Vasc Biol 24: 23–28, 2004.[Abstract/Free Full Text]
  3. Chisolm 3rd GM, Hazen SL, Fox PL, and Cathcart MK. The oxidation of lipoproteins by monocytes-macrophages: biochemical and biological mechanisms. J Biol Chem 274: 2959–25962, 1999.
  4. Dethmers JK and Meister A. Glutathione export by human lymphoid cells: depletion of glutathione by inhibition of its synthesis decreases export and increases sensitivity to irradiation. Proc Natl Acad Sci USA 78: 7492–7496, 1981.[Abstract/Free Full Text]
  5. Gosling J, Slaymaker S, Gu L, Tseng S, Zlot CH, Young SG, Rollins BJ, and Charo IF. MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B. J Clin Invest 103: 773–778, 1999.[ISI][Medline]
  6. Gu L, Okada Y, Clinton SK, Gerard C, Sukhova GK, Libby P, and Rollins BJ. Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol Cell 2: 275–281, 1998.[CrossRef][ISI][Medline]
  7. Ji LL. Antioxidants and oxidative stress in exercise. Proc Soc Exp Biol Med 222: 283–292, 1999.[Abstract/Free Full Text]
  8. Knight JA. Review: Free radicals, antioxidants, and the immune system. Ann Clin Lab Sci 30: 145–158, 2000.[Abstract]
  9. Krenz M, Oldenburg O, Wimpee H, Cohen MV, Garlid KD, Critz SD, Downey JM, and. Benoit JN. Opening of ATP-sensitive potassium channels causes generation of free radicals in vascular smooth muscle cells. Basic Res Cardiol 97: 365–373, 2002.[CrossRef][ISI][Medline]
  10. Lee KW and Lip GYH. Effects of lifesytle on hemostasis, fibrinolysis, and platelet reactivity: a systematic review. Arch Intern Med 163: 2368–2392, 2003.[Abstract/Free Full Text]
  11. Libby P, Ridker PM, and Maseri A. Inflammation and atherosclerosis. Circulation 105: 1135–1143, 2002.[Abstract/Free Full Text]
  12. Liu SS. Generating, partitioning, targeting and functioning of superoxide in mitochondria. Biosci Rep 17: 259–272, 1997.[CrossRef][ISI][Medline]
  13. Liu Y and Gutterman DD. The coronary circulation in diabetes: influence of reactive oxygen species on K+ channel-mediated vasodilation. Vasc Pharmacol 38: 43–49, 2002.
  14. McArdle A, van der Meulen JH, Catapano M, Symons MC, Faulkner JA, and Jackson MJ. Free radical activity following contraction-induced injury to the extensor digitorum longus muscles of rats. Free Radic Biol Med 26: 1085–1091, 1999.[CrossRef][ISI][Medline]
  15. Oliveira HC, Cosso RG, Alberici LC, Maciel EN, Salerno AG, Dorighello GG, Velho JA, de Faria EC, and Vercesi AE. Oxidative stress in atherosclerosis-prone mouse is due to low antioxidant capacity of mitochondria. FASEB J 19: 278–280, 2005.[Abstract/Free Full Text]
  16. Pedersen BK and Hoffman-Goetz L. Exercise and the immune system: regulation, integration, and adaptation. Physiol Rev 80: 1055–1081, 2000.[Abstract/Free Full Text]
  17. Shern-Brewer R, Santanam N, Wetzstein C, White-Welkley J, and Parthasarathy S. Exercise and cardiovascular disease: a new perspective. Arterioscler Thromb Vasc Biol 18: 1181–1187, 1998.[Abstract/Free Full Text]
  18. Siscovick DS, Weiss NS, Fletcher RH, and Lasky T. The incidence of primary cardiac arrest during vigorous exercise. N Engl J Med 311: 984–987, 1984.
  19. Theodorsen L. Evaluation of monocyte counting with two automated instruments by the use of CD 14-specific immunomagnetic Dynabeads. Clin Lab Haematol 17: 225–229, 1995.[ISI][Medline]
  20. Thompson PD. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease. Arterioscler Thromb Vasc Biol 23: 1319–1321, 2003.[Free Full Text]
  21. Urso ML and Clarkson PM. Oxidative stress, exercise, and antioxidant supplementation. Toxicology 189: 41–54, 2003.[CrossRef][ISI][Medline]
  22. Van den Dobbelsteen DJ, Nobel CS, Schlegel J, Cotgreave IA, Orrenius S, and Slater AF. Rapid and specific efflux of reduced glutathione during apoptosis induced by anti-Fas/APO-1 antibody. J Biol Chem 271: 15420–15427, 1996.[Abstract/Free Full Text]
  23. Walrand S, Valeix S, Rodriguez C, Ligot P, Chassagne J, and Vasson MP. Flow cytometry study of polymorphonuclear neutrophil oxidative burst; a comparison of three fluorescent probes. Chin Chim Acta 331: 103–110, 2003.
  24. Wang JS, Lin CC, Chen JK, and Wong MK. Role of chronic exercise in decreasing oxidized LDL-potentiated platelet activation by enhancing platelet-derived NO release and bioactivity in rats. Life Sci 66: 1937–1948, 2000.[CrossRef][ISI][Medline]
  25. Wang JS and Cheng LJ. The effect of strenuous acute exercise on {alpha}2-adrenergic agonist-potentiated platelet activation. Arterioscler Thromb Vasc Biol 19: 1559–1565, 1999.[Abstract/Free Full Text]
  26. Wang JS, Chow SE, Chen JK, and Wong MK. Effects of exercise training on oxidized LDL-mediated platelet function in rats. Thromb Haemost 83: 503–508, 2000.[ISI][Medline]
  27. Wang JS and Huang YH. Effects of exercise intensity on lymphocyte apoptosis induced by oxidative stress in men. Eur J Appl Physiol 95: 290–297, 2005.[CrossRef][ISI][Medline]
  28. Wang JS, Yang CF, Wong MK, Chow SE, and Chen JK. Effect of strenuous arm exercise on oxidized-LDL-potentiated platelet activation in individuals with spinal cord injury. Thromb Haemost 84: 118–123, 2000.[ISI][Medline]
  29. Wang YH, Wang WY, Liao JF, Chen CF, Hou YC, Liou KT, Chou YC, Tien JH, and Shen YC. Prevention of macrophage adhesion molecule-1 (Mac-1)-dependent neutrophil firm adhesion by taxifolin through impairment of protein kinase-dependent NADPH oxidase activation and antagonism of G protein-mediated calcium influx. Biochem Pharmacol 67: 2251–2262, 2004.[CrossRef][ISI][Medline]



This article has been cited by other articles:


Home page
 J. Appl. Physiol.Home page
E. F. Rosa, E. Freymuller, S. S. M. Ihara, J. Aboulafia, and V. L. A. Nouailhetas
Damaging effects of intense repetitive treadmill running on murine intestinal musculature
J Appl Physiol, May 1, 2008; 104(5): 1410 - 1417.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
T. M. Paravicini and R. M. Touyz
NADPH Oxidases, Reactive Oxygen Species, and Hypertension: Clinical implications and therapeutic possibilities
Diabetes Care, February 1, 2008; 31(Supplement_2): S170 - S180.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
J.-S. Wang, H.-Y. Lin, M.-L. Cheng, and M.-K. Wong
Chronic intermittent hypoxia modulates eosinophil- and neutrophil-platelet aggregation and inflammatory cytokine secretion caused by strenuous exercise in men
J Appl Physiol, July 1, 2007; 103(1): 305 - 314.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
101/3/740    most recent
00144.2006v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (7)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, J.-S.
Right arrow Articles by Chow, S.-E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, J.-S.
Right arrow Articles by Chow, S.-E.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2006 by the American Physiological Society.