Hypoxia-induced switches of myosin heavy chain iso-gene expression in rat heart.
Cardiac hypertrophy and atrophy increase expression of fetal iso-genes. A common factor is a decrease in cellular oxygen tension. To test the hypothesis that hypoxia changes cardiac MHC iso-gene expression Wistar rats were exposed to 24 and 48 h of hypobaric hypoxia (11% oxygen) and mRNA was isolated from the left ventricle. In addition, neonatal rat cardiomyocytes were incubated for up to 48 h in a hypoxic chamber. Transcript levels of MHCalpha (adult isoform), MHCbeta (fetal isoform), and Nkx2.5, the earliest known marker for cardiogenesis, were measured by real-time quantitative RT-PCR and normalized to levels of 18S rRNA. Expression of the transcription factor Nkx2.5 increased with hypoxia. Hypoxia decreased MHCalpha and increased MHCbeta transcript levels, both in vivo and in vitro. We conclude that hypoxia per se induces a pattern of isoform gene expression associated with early cardiac development.
Razeghi
Peter
P
Division of Cardiology, Department of Internal Medicine, University of Texas-Houston Medical School, 6431 Fannin, MSB 1.246, 77030, USA.
Essop
M Faadiel
MF
Huss
Janice M
JM
Abbasi
Shahrzad
S
Manga
Nayna
N
Taegtmeyer
Heinrich
H
D000818:Animals; D000831:Animals, Newborn; D015687:Cell Hypoxia; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000254:growth & development; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D029867:Xenopus Proteins
D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D014157:Transcription Factors; D029867:Xenopus Proteins; D018995:Myosin Heavy Chains