title: 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.
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Jung
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Ae Sin
authors.initials: AS
authors.lastname: Lee
authors.forename: Kyung Pyo
authors.initials: KP
authors.lastname: Kang
authors.forename: Sik
authors.initials: S
authors.lastname: Lee
authors.forename: Sung Kwang
authors.initials: SK
authors.lastname: Park
authors.forename: Sang Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: Myung Kwan
authors.initials: MK
authors.lastname: Han
authors.forename: Duk Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Won
authors.initials: W
authors.lastname: Kim
mesh_terms: D000107:Acetylation; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000975:Antioxidants / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002460:Cell Line; D002945:Cisplatin / Q000009:adverse effects*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013267:Stilbenes / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: C550547:6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide; D000970:Antineoplastic Agents; D000975:Antioxidants; D002227:Carbazoles; C498143:RELA protein, human; D013267:Stilbenes; D051996:Transcription Factor RelA; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D002945:Cisplatin; D000077185:Resveratrol