Abstract:
:The beneficial effects of empagliflozin (EMPA) on cardiac functions during ischemia and reperfusion were characterized. The contractile functions of isolated cardiomyocytes from adult C57BL/6J mice were determined with IonOptix SoftEdgeMyoCam system. The mitochondrial superoxide production was measured by MitoSOX fluorescent probe. The ex vivo isolated heart perfusion system was used to determine the pharmacological effects of EMPA on heart's contractile functions under both physiological and pathological conditions. The in vivo regional myocardial ischemia and reperfusion by ligation of left artery coronary artery descending (LAD) was used to measure the myocardial infarction caused by ischemia and reperfusion with or without EMPA treatment. The results demonstrated that EMPA treatment significantly improves cardiomyocyte contractility under hypoxia conditions and augments the post-ischemic recovery in the ex vivo heart perfusion system. Furthermore, the in vivo myocardial infarction measurement shows that EMPA treatment significantly reduce myocardial infarct size caused by ischemia and reperfusion. The biochemical analysis demonstrated that EMPA can trigger cardiac AMPK signaling pathway and attenuate mitochondrial superoxide production under hypoxia and reoxygenation conditions. In conclusion, EMPA can trigger AMPK signaling pathways and modulate myocardial contractility and reduce myocardial infarct size caused by ischemia and reperfusion independent of hypoglycemic effect. The results for the first time demonstrate that the activation of AMPK by EMPA could one reason about EMPA's beneficial effects on heart disease.
journal_name
Mol Cell Endocrinoljournal_title
Molecular and cellular endocrinologyauthors
Lu Q,Liu J,Li X,Sun X,Zhang J,Ren D,Tong N,Li Jdoi
10.1016/j.mce.2019.110642subject
Has Abstractpub_date
2020-02-05 00:00:00pages
110642eissn
0303-7207issn
1872-8057pii
S0303-7207(19)30344-2journal_volume
501pub_type
杂志文章abstract::Ca2+-calmodulin-dependent protein phosphatase activity is found in cytoskeletons of Y-1 mouse adrenal and bovine fasciculata cells. The activity is inhibited by three inhibitors of calmodulin (trifluoperazine, W-7 and pimozide) with EC50 in the low micromolar range. Protein phosphatase activity is inhibited by vanadat...
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journal_title:Molecular and cellular endocrinology
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journal_title:Molecular and cellular endocrinology
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journal_title:Molecular and cellular endocrinology
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doi:10.1016/j.mce.2015.10.021
更新日期:2016-01-05 00:00:00