HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (24) Citing Articles via Google Scholar Google Scholar Articles by Seta, K. A. Articles by Millhorn, D. E. Search for Related Content PubMed PubMed Citation Articles by Seta, K. A. Articles by Millhorn, D. E.

INVITED REVIEW

HIGHLIGHTED TOPICS
Oxygen Sensing in Health and Disease

Functional genomics approach to hypoxia signaling

Department of Genome Science, Genome Research Institute, University of Cincinnati, Cincinnati, Ohio 45237

Mammalian cells require a constant supply of oxygen to maintain energy balance, and sustained hypoxia can result in cell death. It is therefore not surprising that sophisticated adaptive mechanisms have evolved that enhance cell survival during hypoxia. During the past few years, there have been a growing number of reports on hypoxia-induced transcription of specific genes. In this review, we describe a unique experimental approach that utilizes focused cDNA libraries coupled to microarray analyses to identify hypoxia-responsive signal transduction pathways and genes that confer the hypoxia-tolerant phenotype. We have used the subtractive suppression hybridization (SSH) method to create a cDNA library enriched in hypoxia-regulated genes in oxygen-sensing pheochromocytoma cells and have used this library to create microarrays that allow us to examine hundreds of genes at a time. This library contains over 300 genes and expressed sequence tags upregulated by hypoxia, including tyrosine hydroxylase, vascular endothelial growth factor, and junB. Hypoxic regulation of these and other genes in the library has been confirmed by microarray, Northern blot, and real-time PCR analyses. Coupling focused SSH libraries with microarray analyses allows one to specifically study genes relevant to a phenotype of interest while reducing much of the biological noise associated with these types of studies. When used in conjunction with high-throughput, dye-based assays for cell survival and apoptosis, this approach offers a rapid method for discovering validated therapeutic targets for the treatment of cardiovascular disease, stroke, and tumors.

subtractive suppression hybridization; microarray; real-time polymerase chain reaction; RNA interference

This article has been cited by other articles:

				Q. Cheng, T. Nguyen, H. Song, and J. Bonanno Hypoxia Protects Human Corneal Endothelium from Tertiary Butyl Hydroperoxide and Paraquat-Induced Cell Death In Vitro Experimental Biology and Medicine, March 1, 2007; 232(3): 445 - 453. [Abstract] [Full Text] [PDF]

				S. M. Mense, A. Sengupta, M. Zhou, C. Lan, G. Bentsman, D. J. Volsky, and L. Zhang Gene expression profiling reveals the profound upregulation of hypoxia-responsive genes in primary human astrocytes Physiol Genomics, May 16, 2006; 25(3): 435 - 449. [Abstract] [Full Text] [PDF]

				S. Kajimura, K. Aida, and C. Duan Understanding Hypoxia-Induced Gene Expression in Early Development: In Vitro and In Vivo Analysis of Hypoxia-Inducible Factor 1-Regulated Zebra Fish Insulin-Like Growth Factor Binding Protein 1 Gene Expression Mol. Cell. Biol., February 1, 2006; 26(3): 1142 - 1155. [Abstract] [Full Text] [PDF]

				J. Pan, I. Copland, M. Post, H. Yeger, and E. Cutz Mechanical stretch-induced serotonin release from pulmonary neuroendocrine cells: implications for lung development Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L185 - L193. [Abstract] [Full Text] [PDF]

				M. D Ganfornina, M. T Perez-Garcia, G Gutierrez, E Miguel-Velado, J. R Lopez-Lopez, A Marin, D Sanchez, and C Gonzalez Comparative gene expression profile of mouse carotid body and adrenal medulla under physiological hypoxia J. Physiol., July 15, 2005; 566(2): 491 - 503. [Abstract] [Full Text] [PDF]

				F. Mondon, T.-M. Mignot, R. Rebourcet, H. Jammes, J.-L. Danan, F. Ferre, and D. Vaiman Profiling of oxygen-modulated gene expression in early human placenta by systematic sequencing of suppressive subtractive hybridization products Physiol Genomics, June 16, 2005; 22(1): 99 - 107. [Abstract] [Full Text] [PDF]

				M. Steenman, G. Lamirault, N. Le Meur, M. Le Cunff, D. Escande, and J. J. Leger Distinct molecular portraits of human failing hearts identified by dedicated cDNA microarrays Eur J Heart Fail, March 2, 2005; 7(2): 157 - 165. [Abstract] [Full Text] [PDF]

				D. J. Manalo, A. Rowan, T. Lavoie, L. Natarajan, B. D. Kelly, S. Q. Ye, J. G. N. Garcia, and G. L. Semenza Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1 Blood, January 15, 2005; 105(2): 659 - 669. [Abstract] [Full Text] [PDF]

				G. Zhou, T. Golden, I. V. Aragon, and R. E. Honkanen Ser/Thr Protein Phosphatase 5 Inactivates Hypoxia-induced Activation of an Apoptosis Signal-regulating Kinase 1/MKK-4/JNK Signaling Cascade J. Biol. Chem., November 5, 2004; 279(45): 46595 - 46605. [Abstract] [Full Text] [PDF]