TY - JOUR
T1 - Hypoxia-induced alteration of mitochondrial genes in cardiomyocytes
T2 - Role of Bnip3 and Pdk1
AU - Jian, Bixi
AU - Wang, Deli
AU - Chen, Dongquan
AU - Voss, Joachim
AU - Chaudry, Irshad
AU - Raju, Raghavan
PY - 2010/8
Y1 - 2010/8
N2 - The hypoxic conditions induced by reduced blood flow decreases oxygen availability in target tissues. Cellular hypoxia leads to mitochondrial dysfunction, decreased energy production, and increased production of reactive oxygen species. To determine the alteration in expression of mitochondrial genes after hypoxia in cardiomyocytes, we developed a rodent mitochondrial gene chip (RoMitoChip). The chip had 1088 probe sets including 46 probe sets representing 37 mouse mitochondrial DNA transcripts and the remaining probe sets representing mouse nuclear genes contributing to the mitochondrial structure and function. Mouse cardiomyocytes isolated from neonatal C57BL/6 mice that were subjected to hypoxia (1% oxygen) for different time intervals demonstrated a dichotomy in the expression profile of tRNA and mRNA transcripts. We report a total of 483 signature genes that were altered by hypoxia in the cardiac myocytes and related to mitochondrial structure and function. This includes 23 transcripts on mitochondrial DNA. Pathway analysis demonstrated predominant changes in the expression of genes involved in oxidative phosphorylation, glucose and fatty acid metabolism, and apoptosis. The most upregulated genes after 24 h of hypoxia included hypoxia-inducible factor 1, α subunit, inducible genes Bnip3, Pdk1, and Aldoc. Whereas Bnip3 is important in the cardiomyocyte death pathway, Pdk1 enzyme is critical in conserving mitochondrial function by diverting metabolic intermediates to glycolysis. This study identifies the participation of two important pathways, cell death and glycolytic, and two key proteins, Bnip3 and Pdk1, playing critical roles in these pathways in cardiomyocytes after severe hypoxia.
AB - The hypoxic conditions induced by reduced blood flow decreases oxygen availability in target tissues. Cellular hypoxia leads to mitochondrial dysfunction, decreased energy production, and increased production of reactive oxygen species. To determine the alteration in expression of mitochondrial genes after hypoxia in cardiomyocytes, we developed a rodent mitochondrial gene chip (RoMitoChip). The chip had 1088 probe sets including 46 probe sets representing 37 mouse mitochondrial DNA transcripts and the remaining probe sets representing mouse nuclear genes contributing to the mitochondrial structure and function. Mouse cardiomyocytes isolated from neonatal C57BL/6 mice that were subjected to hypoxia (1% oxygen) for different time intervals demonstrated a dichotomy in the expression profile of tRNA and mRNA transcripts. We report a total of 483 signature genes that were altered by hypoxia in the cardiac myocytes and related to mitochondrial structure and function. This includes 23 transcripts on mitochondrial DNA. Pathway analysis demonstrated predominant changes in the expression of genes involved in oxidative phosphorylation, glucose and fatty acid metabolism, and apoptosis. The most upregulated genes after 24 h of hypoxia included hypoxia-inducible factor 1, α subunit, inducible genes Bnip3, Pdk1, and Aldoc. Whereas Bnip3 is important in the cardiomyocyte death pathway, Pdk1 enzyme is critical in conserving mitochondrial function by diverting metabolic intermediates to glycolysis. This study identifies the participation of two important pathways, cell death and glycolytic, and two key proteins, Bnip3 and Pdk1, playing critical roles in these pathways in cardiomyocytes after severe hypoxia.
KW - Heart
KW - apoptosis
KW - custom chip
KW - microarray
KW - mitochip
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UR - http://www.scopus.com/inward/citedby.url?scp=77954966737&partnerID=8YFLogxK
U2 - 10.1097/SHK.0b013e3181cffe7d
DO - 10.1097/SHK.0b013e3181cffe7d
M3 - Article
C2 - 20160671
AN - SCOPUS:77954966737
SN - 1073-2322
VL - 34
SP - 169
EP - 175
JO - Shock
JF - Shock
IS - 2
ER -