Glucose induces apoptosis of cardiomyocytes via microRNA-1 and IGF-1.
Glucose toxicity is an important initiator of cardiovascular disease, contributing to the development of cardiomyocyte death and diabetic complications. The present study investigated whether high glucose state could induce apoptosis of rat cardiomyocyte cell line H9C2 through microRNA regulated insulin-like growth factor (IGF-1) signaling pathway. Our data showed that H9C2 cells exposed to high glucose have increased miR-1 expression level, decreased mitochondrial membrane potential, increased cytochrome-c release, and increased apoptosis. Glucose induced mitochondrial dysfunction, cytochrome-c release and apoptosis was blocked by IGF-1. Using prediction algorithms, we identified 3'-untranslated regions of IGF-1 gene are the target of miR-1. miR-1 mimics, but not mutant miR-1, blocked the capacity of IGF-1 to prevent glucose-induced mitochondrial dysfunction, cytochrome-c release and apoptosis. In conclusion, our data demonstrate that IGF-1 inhibits glucose-induced mitochondrial dysfunction, cytochrome-c release and apoptosis and IGF-1's effect is regulated by miR-1.
Yu
Xi-Yong
XY
Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Provincial Cardiovascular Institute, Guangzhou, Guangdong 510080, PR China. yuxycn@hotmail.com
Song
Yao-Hua
YH
Geng
Yong-Jian
YJ
Lin
Qiu-Xiong
QX
Shan
Zhi-Xin
ZX
Lin
Shu-Guang
SG
Li
Yangxin
Y
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000633:toxicity*; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000201:enzymology / Q000378:metabolism; D009154:Mutation; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D020413:3' Untranslated Regions; D035683:MicroRNAs; D007334:Insulin-Like Growth Factor I; D045304:Cytochromes c; D005947:Glucose