Publication: Role of HSP60 (HSPD1) in diabetes-induced renal tubular dysfunction: Regulation of intracellular protein aggregation, ATP production, and oxidative stress
Issued Date
2017-05-01
Resource Type
ISSN
15306860
08926638
08926638
Other identifier(s)
2-s2.0-85019483496
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
FASEB Journal. Vol.31, No.5 (2017), 2157-2167
Suggested Citation
Siripat Aluksanasuwan, Kanyarat Sueksakit, Kedsarin Fong-Ngern, Visith Thongboonkerd Role of HSP60 (HSPD1) in diabetes-induced renal tubular dysfunction: Regulation of intracellular protein aggregation, ATP production, and oxidative stress. FASEB Journal. Vol.31, No.5 (2017), 2157-2167. doi:10.1096/fj.201600910RR Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/41878
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Role of HSP60 (HSPD1) in diabetes-induced renal tubular dysfunction: Regulation of intracellular protein aggregation, ATP production, and oxidative stress
Other Contributor(s)
Abstract
© FASEB. Because underlying mechanisms of diabetic nephropathy/tubulopathy remained poorly understood, we aimed to define a key protein involving in hyperglycemia-induced renal tubular dysfunction. All altered renal proteins identified from previous large-scale proteome studies were subjected to global protein network analysis, which revealed heat shock protein 60 (HSP60, also known as HSPD1) as the central node of protein-protein interactions. Functional validation was performed using small interfering RNA (siRNA) to knock down HSP60 (siHSP60).At 48 h after exposure to high glucose (HG) (25mM),Madin-Darby canine kidney (MDCK) renal tubular cells transfected with controlled siRNA (siControl) had significantly increased level of HSP60 compared to normal glucose (NG) (5.5 mM), whereas siHSP60-transfected cells showed a dramatically decreased HSP60 level. siHSP60 modestly increased intracellular protein aggregates in both NG and HG conditions. Luciferin-luciferase assay showed that HG modestly increased intracellular ATP, and siHSP60 further enhanced such an increase. OxyBlot assay showed significantly increased level of oxidized proteins in HG-treated siControl-transfected cells, whereas siHSP60 caused marked increase of oxidized proteins under the NG condition. However, the siHSP60-induced accumulation of oxidized proteins was abolished by HG. In summary, our data demonstrated thatHSP60plays roles in regulation of intracellular protein aggregation, ATP production, and oxidative stress in renal tubular cells. Its involvement in HG-induced tubular cell dysfunction was most likely via regulation of intracellular ATP production.