Overexpressed SIRT6 attenuates cisplatin-induced acute kidney injury by inhibiting ERK1/2 signaling
| Autor: | Sen Zhao, Zhongchi Li, Gabriel Amador, Yanying Wang, Liyuan Li, Zhao Wang, Nannan Zhang, Kang Xu, Ying Qiu |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine SIRT6 Mice 129 Strain Apoptosis Inflammation Kidney Gene Expression Regulation Enzymologic Histones 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Animals Sirtuins Medicine Promoter Regions Genetic Cells Cultured Cell Proliferation Mice Knockout Mitogen-Activated Protein Kinase 1 Cisplatin Binding Sites Mitogen-Activated Protein Kinase 3 biology business.industry Acute kidney injury NF-κB Acute Kidney Injury medicine.disease Up-Regulation Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure chemistry Nephrology 030220 oncology & carcinogenesis Sirtuin biology.protein Cancer research Inflammation Mediators medicine.symptom Apoptosis Regulatory Proteins business Signal Transduction medicine.drug |
| Zdroj: | Kidney International. 93:881-892 |
| ISSN: | 0085-2538 |
| Popis: | Sirtuin 6 (SIRT6) is a NAD+-dependent deacetylase associated with numerous aspects of health and physiology. Overexpression of SIRT6 has emerged as a protector in cardiac tissues against pathologic cardiac hypertrophy. However, the mechanism of this protective effect is not fully understood. Here, both in vivo and in vitro results demonstrated that SIRT6 overexpression can attenuate cisplatin-induced kidney injury in terms of renal dysfunction, inflammation and apoptosis. In addition, SIRT6 knockout aggravated kidney injury caused by cisplatin. We also found that SIRT6 bound to the promoters of ERK1 and ERK2 and deacetylated histone 3 at Lys9 (H3K9) thereby inhibiting ERK1/2 expression. Furthermore, inhibition of ERK1/2 activity eliminated aggravation of kidney injury caused by SIRT6 knock out. Thus, our findings uncover the protective effect of SIRT6 on the kidney and define a new mechanism by which SIRT6 regulates inflammation and apoptosis. This may provide a new therapeutic target for kidney injury under stress. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|