Oncostatin M (OSM) protects against cardiac ischaemia/reperfusion injury in diabetic mice by regulating apoptosis, mitochondrial biogenesis and insulin sensitivity.
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 (IP7) production, thus activating PI3K/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 IP7 production, enhanced cardiomyocyte apoptosis, impaired mitochondrial biogenesis, glucose homoeostasis and insulin sensitivity in cardiac I/R injured diabetic mice. Inhibition of IP7 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 IP7/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 IP7 production.
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Dongdong
D
Sun
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Shuang
S
Li
Department of Toxicology, School of Public Health, Fourth Military Medical University, Xi'an, China.
Hao
H
Wu
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Mingming
M
Zhang
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Xiaotian
X
Zhang
Department of Cardiology, Tianjin Union Medicine Center, Tianjin, China.
Liping
L
Wei
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Xing
X
Qin
Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA, USA.
Erhe
E
Gao
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000503:physiopathology*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics; D007295:Inositol Phosphates / Q000037:antagonists & inhibitors / Q000378:metabolism; D007333:Insulin Resistance; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D053683:Oncostatin M / Q000494:pharmacology*; D001678:Organelle Biogenesis; D020011:Protective Agents / Q000494:pharmacology; D053677:Receptors, Oncostatin M / Q000235:genetics / Q000378:metabolism
D007295:Inositol Phosphates; D020011:Protective Agents; D053677:Receptors, Oncostatin M; D053683:Oncostatin M; D005947:Glucose
diabetes; inositol pyrophosphate 7; ischaemia/Reperfusion injury; oncostatin M