N-acetylcysteine protects septic acute kidney injury by inhibiting SIRT۳-mediated mitochondrial dysfunction and apoptosis
Publish place: Iranian Journal of Basic Medical Sciences، Vol: 27، Issue: 7
Publish Year: 1403
نوع سند: مقاله ژورنالی
زبان: English
View: 32
This Paper With 7 Page And PDF Format Ready To Download
- Certificate
- من نویسنده این مقاله هستم
استخراج به نرم افزارهای پژوهشی:
شناسه ملی سند علمی:
JR_IJBMS-27-7_008
تاریخ نمایه سازی: 18 اردیبهشت 1403
Abstract:
Objective(s): To investigate the protective effect of N-acetylcysteine (NAC) on septic acute kidney injury (SAKI) via regulating Sirtuin۳ (SIRT۳)-mediated mitochondrial dysfunction and apoptosis.Materials and Methods: By constructing SIRT۳ knockout mice and culturing kidney tubular epithelial cells (KTECs), we assessed the changes of renal function and detected the protein expression of adenine nucleotide translocator (ANT), cyclophilin (CypD) and voltage-dependent anion channel (VDAC) using western-blotting, and simultaneously detected toll-like receptor ۴ (TLR۴), inhibitor of kappa B kinase (IKKβ), inhibitor of Kappa Bα (IκBα), and p۶۵ protein expression. We observed mitochondrial damage of KTECs using a transmission electron microscope and assessed apoptosis by TdT-mediated dUTP Nick-End Labeling and flow cytometry. Results: SIRT۳ deficiency led to the deterioration of renal function, and caused a significant increase in inducible nitric oxide synthase production, a decrease in mitochondrial volume, up-regulation of TLR۴, IκBα, IKKβ, and p۶۵ proteins, and up-regulation of ANT, CypD and VDAC proteins. However, NAC significantly improved renal function and down-regulated the expression of TLR۴, IκBα, IKKβ, and p۶۵ proteins. Furthermore, SIRT۳ deficiency led to a significant increase in KTEC apoptosis, while NAC up-regulated the expression of SIRT۳ and inhibited apoptosis.Conclusion: NAC has a significant protective effect on SAKI by inhibiting SIRT۳-mediated mitochondrial dysfunction and apoptosis of KTECs.
Keywords:
Authors
Heng Fan
Department of Intensive Care Unit, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, P.R China
Le Jian-wei
Department of Intensive Care Unit, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, P.R China
sun Min
Department of Intensive Care Unit, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, P.R China
Zhu Jian-hua
Department of Intensive Care Unit, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, P.R China
مراجع و منابع این Paper:
لیست زیر مراجع و منابع استفاده شده در این Paper را نمایش می دهد. این مراجع به صورت کاملا ماشینی و بر اساس هوش مصنوعی استخراج شده اند و لذا ممکن است دارای اشکالاتی باشند که به مرور زمان دقت استخراج این محتوا افزایش می یابد. مراجعی که مقالات مربوط به آنها در سیویلیکا نمایه شده و پیدا شده اند، به خود Paper لینک شده اند :