Open AccessOncostatin M ( OSM ) protects against cardiac ischaemia/reperfusion injury in diabetic mice by regulating apoptosis, mitochondrial biogenesis and insulin sensitivity
Author(s) -
Sun Dongdong,
Li Shuang,
Wu Hao,
Zhang Mingming,
Zhang Xiaotian,
Wei Liping,
Qin Xing,
Gao Erhe
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12501
Subject(s) - mitochondrial biogenesis , diabetic cardiomyopathy , protein kinase b , endocrinology , mitochondrion , medicine , biology , chemistry , microbiology and biotechnology , signal transduction , cardiomyopathy , heart failure
Oncostatin M ( OSM ) exhibits many unique biological activities by activating Oβ receptor. However, its role in myocardial I/R injury in diabetic mice remains unknown. The involvement of OSM was assessed in diabetic mice which underwent myocardial I/R injury by OSM treatment or genetic deficiency of OSM receptor Oβ. Its mechanism on cardiomyocyte apoptosis, mitochondrial biogenesis and insulin sensitivity were further studied. OSM alleviated cardiac I/R injury by inhibiting cardiomyocyte apoptosis through inhibition of inositol pyrophosphate 7 ( IP 7) production, thus activating PI 3K/Akt/ BAD pathway, decreasing Bax expression while up‐regulating Bcl‐2 expression and decreasing the ratio of Bax to Bcl‐2 in db/db mice. OSM enhanced mitochondrial biogenesis and mitochondrial function in db/db mice subjected to cardiac I/R injury. On the contrary, OSM receptor Oβ knockout exacerbated cardiac I/R injury, increased IP 7 production, enhanced cardiomyocyte apoptosis, impaired mitochondrial biogenesis, glucose homoeostasis and insulin sensitivity in cardiac I/R injured diabetic mice. Inhibition of IP 7 production by TNP (IP6K inhibitor) exerted similar effects of OSM . The mechanism of OSM on cardiac I/R injury in diabetic mice is partly associated with IP 7/Akt and adenine mononucleotide protein kinase/ PGC ‐1α pathway. OSM protects against cardiac I/R Injury by regulating apoptosis, insulin sensitivity and mitochondrial biogenesis in diabetic mice through inhibition of IP 7 production.