Abstract
BackgroundSirtuin 3 (Sirt3) is a key regulator of energy metabolism and oxidative stress. To investigate the role of Sirt3 in contrast-induced acute kidney injury (CIAKI), we established the model both in vivo and in vitro to explore the potential mechanisms.MethodsIn vivo, we established CIAKI models in wild-type (WT) and Sirt3-knockout (Sirt3-KO) mice. Blood urea nitrogen (BUN) and serum creatinine (Scr) were detected by enzyme-linked immunosorbent assay, Glomerular Filtration Rate (GFR) and creatinine clearance were also investigated. We detected the production of reactive oxygen species (ROS) via 2′7′-dichlorodihydro-fluorescein diacetate. The expressions of Sirt3, oxidative stress and apoptosis related markers (MnSOD, Catalase, Acetyl-MnSOD K68, Nox4, Bax, Bcl-2 and Caspase3) were measured and analyzed. In addition, we observed the effect of nicotinamide riboside (NR) on CIAKI in WT and Sirt3-KO mice. In vitro, Sirt3 was knocked out by siRNA transfection method in HK-2 cells. Sirt3, ROS, oxidative stress and apoptosis markers in HK-2 cells were also measured.ResultsOur data demonstrated that the levels of Scr and BUN in Sirt3-KO mice were increased while the levels of the GFR and creatinine clearance were decreased in CIAKI mice. In Sirt3-KO or siRNA groups, the activities of MnSOD and Catalase were markedly down-regulated. Also, the expression of Caspase3 were markedly increased and the ratio of Bcl-2/Bax was decreased, while the ROS level was increased in Sirt3 deficiency groups. NR ameliorated CIAKI in WT mice but not in Sirt3-KO mice.ConclusionOur results suggest that Sirt3 deficiency aggravates contrast-induced acute kidney injury. Sirt3 is critical in NR-mediated renoprotection in CIAKI.
Highlights
Sirtuin 3 (Sirt3) is a key regulator of energy metabolism and oxidative stress
Sirt3 protein expression increased in contrast‐induced acute kidney injury in vivo and in vitro First, we tested the sirt3 expression in contrast-induced acute kidney injury model in vivo and in vitro
We found that Ioversol treatment significantly increase the Sirt3 expression in WT mice (Fig. 1a) and HK-2 cells (Fig. 1b), suggesting the potential role of Sirt3 in contrast-induced acute kidney injury (CIAKI)
Summary
To investigate the role of Sirt in contrast-induced acute kidney injury (CIAKI), we established the model both in vivo and in vitro to explore the potential mechanisms. Sirt has been found to play important roles in maintaining mitochondrial function and integrity in response to the oxidative stress. Morigi et al found that activation of Sirt attenuates mitochondrial dysfunction in cisplatin-induced acute kidney injury [7], and the results were confirmed by Liu et al [8]. Another study found Sirt prevents renal tubulointerstitial fibrosis by ameliorating oxidative stress and mitochondrial dysfunction in an angiotensin II-induced kidney injury model [9]. Our newly study found Sirt activation ameliorates kidney injury induced by hypertension [10]. Whether endogenous Sirt play a protective role in CIAKI is still unclear. The results show for the first time whether endogenous Sirt produces protection against CIAKI in mice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
