Effects of diazoxide on streptozotocin induced β cell damage via HSP70/HSP90/TLR4/AMPK signaling pathways.

IF 1.6 4区 生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Salih Tunc Kaya
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引用次数: 0

Abstract

I investigated the effects of diazoxide, a mitochondrial potassium channel opener, on streptozotocin (STZ) induced pancreatic β cell damage via the HSP70/HSP90/TLR4/AMPK signaling pathways in vitro. I used the pancreatic β cell line, 1.1B4, to create four groups: control, STZ treated, diazoxide treated, STZ + diazoxide treated. The STZ treated cells were exposed to 20 µM STZ for 2 h with or without 100 µM diazoxide for 24 h. Total antioxidant status (TAS), total oxidant status (TOS), cell viability and mitochondrial membrane potential (MMP) were measured. Expression of ATP-sensitive potassium channel (KATP) subunits, heat shock protein-70 (HSP70), heat shock protein-90 (HSP90), toll-like receptor 4 (TLR4), AMP-activated protein kinase (AMPK) and some apoptotic proteins were detected using western blotting. Apoptosis was assessed using TUNEL staining. STZ increased TOS and OSI in the pancreatic β cells; however, diazoxide failed to improve oxidative stress. Also, STZ increased tunnel positive cells in the pancreatic β cells. Diazoxide decreased the tunnel positive cells in the STZ treated β cell. STZ decreased MMP; however, diazoxide did not normalize MMP in the STZ induced β cells. Diazoxide increased the HSP70:HSP90 protein expression ratio. STZ decreased expression of AMPK and subunits of KATP channel and increased the expression of caspase-3 and TLR4 protein; diazoxide normalized the expression of all proteins studied. KATP channel opening by diazoxide protects pancreatic β cells against STZ toxicity via HSP70/HSP90/TLR4/AMPK signaling.

二氮氧化物通过HSP70/HSP90/TLR4/AMPK信号通路对链脲佐菌素诱导的β细胞损伤的影响
研究了线粒体钾通道打开剂二氮氧化物通过HSP70/HSP90/TLR4/AMPK信号通路对链脲佐菌素(STZ)诱导的胰腺β细胞损伤的影响。我使用胰腺β细胞系1.1B4,创建四组:对照组,STZ处理,二氮氧化合物处理,STZ +二氮氧化合物处理。将STZ处理的细胞分别暴露于20µM STZ中2 h,加或不加100µM二氮氧化物24 h。测定总抗氧化状态(TAS)、总氧化状态(TOS)、细胞活力和线粒体膜电位(MMP)。western blotting检测atp敏感钾通道(KATP)亚基、热休克蛋白-70 (HSP70)、热休克蛋白-90 (HSP90)、toll样受体4 (TLR4)、amp活化蛋白激酶(AMPK)及部分凋亡蛋白的表达。TUNEL染色检测细胞凋亡。STZ增加胰腺β细胞的TOS和OSI;然而,二氮氧化物未能改善氧化应激。STZ还增加了胰腺β细胞中的隧道阳性细胞。二氮氧化物使STZ处理的β细胞隧道阳性细胞减少。STZ降低MMP;然而,二氮氧化物不能使STZ诱导的β细胞中的MMP正常化。二氮氧化物增加了HSP70:HSP90蛋白的表达比。STZ降低AMPK和KATP通道亚基的表达,增加caspase-3和TLR4蛋白的表达;二氮氧化物使所研究的所有蛋白的表达正常化。二氮氧化物通过HSP70/HSP90/TLR4/AMPK信号通路打开KATP通道,保护胰腺β细胞免受STZ毒性。
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来源期刊
Biotechnic & Histochemistry
Biotechnic & Histochemistry 生物-生物工程与应用微生物
CiteScore
3.40
自引率
6.20%
发文量
46
审稿时长
6-12 weeks
期刊介绍: Biotechnic & Histochemistry (formerly Stain technology) is the official publication of the Biological Stain Commission. The journal has been in continuous publication since 1926. Biotechnic & Histochemistry is an interdisciplinary journal that embraces all aspects of techniques for visualizing biological processes and entities in cells, tissues and organisms; papers that describe experimental work that employs such investigative methods are appropriate for publication as well. Papers concerning topics as diverse as applications of histochemistry, immunohistochemistry, in situ hybridization, cytochemical probes, autoradiography, light and electron microscopy, tissue culture, in vivo and in vitro studies, image analysis, cytogenetics, automation or computerization of investigative procedures and other investigative approaches are appropriate for publication regardless of their length. Letters to the Editor and review articles concerning topics of special and current interest also are welcome.
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