Differentially regulated functional gene clusters identified in early hypoxic cardiomyocytes.
Pathological stress including myocardial infarction and hypertension causes a negative effect on calcium regulation and homeostasis. Nevertheless, few studies reveal that Ca(2+) regulatory genes are related to pathological status in cardiomyocytes under early hypoxia. To determine the alteration of Ca(2+)-related gene in hypoxic myocytes, primary neonatal rat ventricular cardiomyocytes (NRVCMs) was isolated. Survival of hypoxic NRVCMs was significantly decreased in 6 h. We confirmed an increase of reactive oxygen species (ROS) generation and Ca(2+) overload in hypoxic NRVCMs by using 2',7'-dichlorodihydro-fluorescein diacetate (H2DCFDA) and FACS analysis. Furthermore, survival/apoptotic signals were also regulated in same condition. The expression profiles of more than 30,000 genes from NRVCMs that were subjected to early hypoxia revealed 630 genes that were differentially regulated. The intracellular Na(+) overload and Ca(2+) handling genes with at least two-fold changes were confirmed. The levels of Ca(2+)-handling proteins (calsequestrin, calmodulin, and calreticulin), ion channels (NCX, Na(+)-K(+)-ATPase, SERCA2a, and PLB), and stress markers (RyR2, ANP, and BNP) were significantly altered in early hypoxia. These results demonstrate that early hypoxia alters Ca(2+)-related gene expression in NRVCMs, leading to pathological status.
Division of Thoracic and Cardiovascular Surgery, National Health Insurance Cooperated Ilsan Hospital, 100 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeongi-do, Republic of Korea.
Do Kyun
DK
Kim
Eunmi
E
Choi
Byeong-Wook
BW
Song
Min-Ji
MJ
Cha
Onju
O
Ham
Se-Yeon
SY
Lee
Chang Youn
CY
Lee
Jun-Hee
JH
Park
Heesang
H
Song
Ki-Chul
KC
Hwang
D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D016000:Cluster Analysis; D005786:Gene Expression Regulation; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D059467:Transcriptome
D002135:Calcium-Binding Proteins; D007473:Ion Channels; D009124:Muscle Proteins