Dexmedetomidine alleviates CoCl2-induced hypoxic cellular damage in INS-1 cells by regulating autophagy.

IF 4.2 4区 医学 Q1 ANESTHESIOLOGY
Jin Ha Park, Ju Eun Oh, Namo Kim, Young-Lan Kwak
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Abstract

Background: Ischemia-reperfusion (I/R) injury is inevitable during the perioperative period. The pancreas is susceptible to I/R injury. Autophagy, a self-digestion process, is upregulated during I/R injury and strongly induced by hypoxia. This study aims to determine whether dexmedetomidine can decrease pancreatic β-cell damage by regulating autophagy under hypoxia.

Methods: INS-1 rat insulinoma cells were cultured in dexmedetomidine before being exposed to cobalt chloride (CoCl2)-induced hypoxia. Cell viability and the expression of autophagy-related proteins (light chain 3B [LC3B]-II, p62, and ATGs) were assessed. The expression of apoptosis-related proteins (BCL-2 and P-BAD) were also evaluated. CoCl2-treated INS-1 cells were pretreated with the autophagosome formation inhibitor, 3-methyladenine (3-MA), to compare its effects with those of dexmedetomidine. Bafilomycin-A1 (Baf-A1) that inhibits autophagosome degradation was used to confirm the changes in autophagosome formation induced by dexmedetomidine.

Results: Dexmedetomidine attenuated the increased expression of autophagic proteins (LC3B-II, p62, and ATGs) and reversed the CoCl2-induced reduction in the proliferation of INS-1 cells after hypoxia. Dexmedetomidine also alleviated the decreased expression of the anti-apoptotic protein (BCL-2) and the increased expression of apoptotic protein (BAX). Dexmedetomidine reduces the activation of autophagy through inhibiting autophagosome formation, as confirmed by a decrease in LC3B-II/I ratio, a marker of autophagosome formation, in LC3B turnover assay combined with Baf-A1.

Conclusions: Dexmedetomidine alleviates the degree of cellular damage in INS-1 cells against CoCl2-induced hypoxia by regulating autophagosome formation. These results provide a basis for further studies to confirm these effects in clinical practice.

右美托咪定通过调节自噬减轻CoCl2-诱导的INS-1细胞缺氧性细胞损伤。
背景:在围手术期,缺血再灌注(I/R)损伤不可避免。胰腺很容易受到 I/R 损伤。自噬是一种自我消化过程,在 I/R 损伤期间上调,并在缺氧时被强烈诱导。本研究旨在确定右美托咪定是否能在缺氧条件下通过调节自噬减少胰腺β细胞损伤:方法:在氯化钴(CoCl2)诱导的缺氧条件下,用右美托咪定培养 INS-1 大鼠胰岛素瘤细胞。评估细胞活力和自噬相关蛋白(轻链 3B [LC3B]-II、p62 和 ATGs)的表达。同时还评估了细胞凋亡相关蛋白(BCL-2 和 P-BAD)的表达。用自噬体形成抑制剂 3-甲基腺嘌呤(3-MA)预处理经 CoCl2 处理的 INS-1 细胞,以比较其与右美托咪定的作用。用抑制自噬体降解的巴非洛霉素-A1(Baf-A1)来证实右美托咪定诱导的自噬体形成的变化:结果:右美托咪定减轻了自噬蛋白(LC3B-II、p62和ATGs)表达的增加,并逆转了CoCl2诱导的INS-1细胞缺氧后增殖的减少。右美托咪定还缓解了抗凋亡蛋白(BCL-2)表达的减少和凋亡蛋白(BAX)表达的增加。右美托咪定通过抑制自噬体的形成来减少自噬的激活,这一点通过结合 Baf-A1 的 LC3B 翻转试验中作为自噬体形成标志的 LC3B-II/I 比值的降低得到了证实:结论:右美托咪定通过调节自噬体的形成减轻了INS-1细胞对CoCl2诱导的缺氧的细胞损伤程度。这些结果为在临床实践中证实这些作用提供了进一步研究的基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
6.20
自引率
6.90%
发文量
84
审稿时长
16 weeks
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