Thapalia, BA and Zhou, Z and Lin, X, Sauchinone augments cardiomyocyte viability by enhancing autophagy proteins -PI3K, ERK(1/2), AMPK and Beclin-1 during early ischemia-reperfusion injury in vitro, American Journal of Translational Research, 8, (7) pp. 3251-3265. ISSN 1943-8141 (2016) [Refereed Article]
Copyright 2016 American Journal of Translational Research. Licensed under Creative Commons Attribution Noncommercial License (CC BY-NC)
Official URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC49694...
Background: Sauchinone has proved its anti-oxidant and anti-inflammatory properties in various animal tissues. This study sought to illustrate its regulatory nature on autophagy associated proteins (PI3K, ERK1/2, AMPK, and Beclin-1) during early cardiomyocyte ischemia and subsequent reperfusion.
Methods: Cultured cardiomyocytes were subjected to simulated Ischemia/reperfusion with and without Sauchinone pretreatment and also in the presence of autophagy inhibitor (3-MA). Colorimetric analysis of CCK-8, LDH antibody assay as well as Western blot analysis were performed to observe the expressions of LC3B (II) and Beclin-1 protein (markers of autophagy), autophagy proteins (PI3K, ERK1/2 and AMPK) and apoptotic proteins (Bax and Bcl-2) and the results were quantified into their grey values and subjected to statistical analysis.
Results: demonstrated cell survival enhancing properties with increase in CCK-8 (SD = 0.553▒0.012) and decrease in LDH (SD = 0.183▒0.054) expressions, both of which were best observed at test dose of 20 Ámol/L. At this dose, there was increment in cellular autophagy as demonstrated by peaking of autophagy markers LC3B-II (p<0.05) and Beclin-1 (p<0.05) with strong correlations (r = 0.99). Similarly, the autophagy proteins, compared to control and I/R model, also showed a significant increased level with PI3K (p<0.0001), total p-ERK1/2 (p<0.0001) and p-AMPKα (p<0.0001). Simultaneously, a decrease in expressions of pro-apoptotic molecules Bax (r = 0.989, p<0.0001) with increment of in the anti-apoptotic protein Bcl-2 (r = 0.996, p<0.0001) was observed. The observed effects on cell density, viability and autophagy was abrogated in presence of 3-MA.
Conclusions: enhances cell survival by promoting autophagy and inhibiting apoptosis in cardiomyocytes during early stages of Ischemia/reperfusion injury.
|Item Type:||Refereed Article|
|Keywords:||sauchinone, autophagy protein, ischemia-reperfusion injury, apoptosis|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Pharmacology and pharmaceutical sciences|
|Research Field:||Basic pharmacology|
|Objective Group:||Clinical health|
|Objective Field:||Efficacy of medications|
|UTAS Author:||Zhou, Z (Dr Zhen Zhou)|
|Web of Science® Times Cited:||8|
|Deposited By:||Menzies Institute for Medical Research|
|Downloads:||5 View Download Statistics|
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