Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 13, Issue 6, Pages 7694-7709Publisher
MDPI AG
DOI: 10.3390/ijms13067694
Keywords
heart; ischemia/reperfusion; mitochondria; metformin; AMPK; PPAR alpha
Funding
- University of Puerto Rico School of Medicine
- National Center for Research Resources, National Institutes of Health [2G12-RR003051]
- American Physiological Society
Ask authors/readers for more resources
Metformin, an anti-diabetic drug, exerts cardioprotection against ischemia-reperfusion (IR) through the activation of AMPK. However, the molecular mechanisms underlying these beneficial effects remain elusive. In this study, we examined the role of PPAR alpha in mediating cardioprotective effects of metformin on mitochondria. Hearts of male Sprague-Dawley rats perfused by Langendorff were subjected to IR in the presence or absence of metformin and the PPAR alpha inhibitor, GW6471. IR reduced cardiac function and compromised the structural integrity of cardiac cells evidenced by increased LDH release from the hearts. In addition, IR induced mitochondrial dysfunction as evidenced by reduced respiration and increased mitochondrial permeability transition pore (PTP) opening. However, metformin-treated hearts demonstrated improved post-ischemic recovery of cardiac function and reduced cell death that were associated with increased state 3 respiration at complexes I and II (by 27% and 32%, respectively, both p < 0.05) and decreased PTP opening (by 27%, p < 0.05) compared to untreated hearts. The protective effects of metformin on cardiac function and mitochondria were blocked by GW6471. Thus, our results demonstrate that inhibition of PPARa attenuates the beneficial effects of metformin on mitochondria in acute IR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available