Regulation of gene expression for neurotransmitters during adaptation to hypoxia in oxygen-sensitive neuroendocrine cells.
Reduced oxygen tension (hypoxia) in the environment stimulates oxygen-sensitive cells in the carotid body (CB). Upon exposure to hypoxia, the CB immediately triggers a reflexive physiological response, thereby increasing respiration. Adaptation to hypoxia involves changes in the expression of various CB genes, whose products are involved in the transduction and modulation of the hypoxic signal to the central nervous system (CNS). Genes encoding neurotransmitter-synthesizing enzymes and receptors are particularly important in this regard. The cellular response to hypoxia correlates closely with the release and biosynthesis of catecholamines. The gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme for catecholamine biosynthesis, is regulated by hypoxia in the CB and in the oxygen-sensitive cultured PC12 cell line. Recently, genomic microarray studies have identified additional genes regulated by hypoxia. Patterns of gene expression vary, depending on the type of applied hypoxia, e.g., intermittent vs. chronic. Construction of a hypoxia-regulated, CB-specific, subtractive cDNA library will enable us to further characterize regulation of gene expression in the CB.
Paulding
Waltke R
WR
Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0576, USA.
Schnell
Phillip O
PO
Bauer
Amy L
AL
Striet
Justin B
JB
Nash
James A
JA
Kuznetsova
Anna V
AV
Czyzyk-Krzeska
Maria F
MF
D000222:Adaptation, Physiological; D000818:Animals; D001483:Base Sequence; D002344:Carotid Body / Q000378:metabolism*; D002395:Catecholamines / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D010100:Oxygen / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D014158:Transcription, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D002395:Catecholamines; D014446:Tyrosine 3-Monooxygenase; D010100:Oxygen