SIRT1 overexpression decreases cisplatin-induced acetylation of NF-κB p65 subunit and cytotoxicity in renal proximal tubule cells.
ABSTRACT As the increased acetylation of p65 is linked to nuclear factor-κB (NF-κB) activation, the regulation of p65 acetylation can be a potential target for the treatment of inflammatory injury. Cisplatin-induced nephrotoxicity is an important issue in chemotherapy of cancer patients. SIRT1, nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylase, has been implicated in a variety of cellular processes such as inflammatory injury and the control of multidrug resistance in cancer. However, there is no report on the effect of SIRT1 overexpression on cisplatin-induced acetylation of p65 subunit of NF-κB and cell injury. To investigate the effect of SIRT1 in on cisplatin-induced acetylation of p65 subunit of NF-κB and cell injury, HK2 cells were exposed with SIRT1 overexpression, LacZ adenovirus or dominant negative adenovirus after treatment with cisplatin. While protein expression of SIRT1 was decreased by cisplatin treatment compared with control buffer treatment, acetylation of NF-κB p65 subunit was significantly increased after treatment with cisplatin. Overexpression of SIRT1 ameliorated the increased acetylation of p65 of NF-κB during cisplatin treatment and cisplatin-induced cytotoxicity. Further, treatment of cisplatin-treated HK2 cells with resveratrol, a SIRT1 activator, also decreased acetylation of NF-κB p65 subunit and cisplatin-induced increase of the cell viability in HK2 cells. Our findings suggests that the regulation of acetylation of p65 of NF-κB through SIRT1 can be a possible target to attenuate cisplatin-induced renal cell damage.
Article: Role of sirtuins in kidney disease.[Show abstract] [Hide abstract]
ABSTRACT: Accumulating evidence indicates the beneficial effects of sirtuins (SIRTs), including SIRT1 and SIRT3, which are NAD-dependent deacetylases, in age-related diseases such as diabetes, neuron disease, cardiovascular disease and kidney disease. SIRT1 deacetylates many targets, such as transcriptional factors and proteins, and exhibits renoprotection through reduction of fibrosis, antiapoptotic and anti-inflammatory effects and induction of autophagy in renal cells. SIRT1 may also participate in the regulation of blood pressure by sodium handling and by decreasing the responsiveness for angiotensin II. However, SIRT1 may be involved in the progression of cyst formation of renal epithelial cells in autosomal-dominant polycystic kidney disease (ADPKD). SIRT3 protects renal tubular cells against palmitate-induced lipotoxicity through antioxidative and anti-inflammatory effects. The activation of SIRT1 and SIRT3 may be a novel therapeutic strategy for kidney diseases, but not for ADPKD.Current Opinion in Nephrology and Hypertension 11/2013; · 3.96 Impact Factor
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ABSTRACT: Chronic inflammation is a major biological mechanism underpinning biological ageing process and age-related diseases. Inflammation is also the key response of host defense against pathogens and tissue injury. Current opinion sustains that during evolution the host defense and ageing process have become linked together. Thus, the large array of defense factors and mechanisms linked to the NF-kappaB system seem to be involved in ageing process. This concept leads us in proposing inductors of NF-kappaB signaling pathway as potential ageing biomarkers. On the other hand, ageing biomarkers, represented by biological indicators and selected through apposite criteria, should help to characterize biological age and, since age is a major risk factor in many degenerative diseases, could be subsequently used to identify individuals at high risk of developing age-associated diseases or disabilities. In this report, some inflammatory biomarkers will be discussed for a better understanding of the concept of biological ageing, providing ideas on eventual working hypothesis about potential targets for the development of new therapeutic strategies and improving, as consequence, the quality of life of elderly population.Immunity & Ageing 06/2013; 10(1):24.
Dataset: nf-kb paper