Effects of diazoxide on streptozotocin induced beta cell damage via HSP70/HSP90/TLR4/AMPK signaling pathways
Yükleniyor...
Dosyalar
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Taylor & Francis Ltd
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
I investigated the effects of diazoxide, a mitochondrial potassium channel opener, on streptozotocin (STZ) induced pancreatic beta cell damage via the HSP70/HSP90/TLR4/AMPK signaling pathways in vitro. I used the pancreatic beta cell line, 1.1B4, to create four groups: control, STZ treated, diazoxide treated, STZ + diazoxide treated. The STZ treated cells were exposed to 20 mu M STZ for 2 h with or without 100 mu M 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 (K-ATP) 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 beta cells; however, diazoxide failed to improve oxidative stress. Also, STZ increased tunnel positive cells in the pancreatic beta cells. Diazoxide decreased the tunnel positive cells in the STZ treated beta cell. STZ decreased MMP; however, diazoxide did not normalize MMP in the STZ induced beta cells. Diazoxide increased the HSP70:HSP90 protein expression ratio. STZ decreased expression of AMPK and subunits of K-ATP channel and increased the expression of caspase-3 and TLR4 protein; diazoxide normalized the expression of all proteins studied. K-ATP channel opening by diazoxide protects pancreatic beta cells against STZ toxicity via HSP70/HSP90/TLR4/AMPK signaling.
Açıklama
Anahtar Kelimeler
Atp; Diabetes; Diazoxide; Hsp70; Hsp90; Human; Potassium Channel; Streptozotocin, Pancreatic-Islet; Atp; Protection; Mitochondria; Expression; Improves; Neurons; Stress
Kaynak
Biotechnic & Histochemistry
WoS Q Değeri
Q4
Scopus Q Değeri
Q2
