title: Protective functions of peroxiredoxin-1 against cytokine-induced MIN6 pancreatic β-cell line death.
abstract: Pancreatic β-cells play a crucial role in glucose homeostasis, and the failure of these cells to function results in the development of type 1 diabetes (T1D). The MIN6 cell line, which closely resembles pancreatic β-cells, was used to unravel the relationship between pancreatic β-cell function and the antioxidant enzyme PRX-1. PRX-1 was knocked down in MIN6 cells using a shPRX-1 lentiviral construct, and a mixture of inflammatory cytokines was administered to challenge the MIN6 cells. Nitric oxide (NO) production and inducible NO synthase (iNOS) expression were elevated in shPRX-1 compared with the control. Also, shPRX-1 transduced cells showed higher levels of NF-κB nuclear translocation, suggesting that PRX-1 has a regulatory role in NF-κB nuclear translocation and iNOS expression. In correlation with NO levels, decreased anti-apoptotic gene Bcl-xl level and elevated pro-apoptotic gene Bim levels were observed in shPRX-1 cells compared with scramble, and cell viability decreased accordingly. A rescue experiment was performed subsequently using an iNOS inhibitor to confirm NO as the cause of cell death. Overall, the results of this study suggest possible protective roles of the antioxidant enzyme PRX-1 in the insulinoma cell line MIN6 and possibly in pancreatic β-cells under T1D conditions.
authors.affiliation: a Laboratory of Host Defense Modulation, College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Lee
authors.forename: Dong Sup
authors.initials: DS
authors.lastname: Song
authors.forename: Jong-Sun
authors.initials: JS
authors.lastname: Yoo
authors.forename: Kyeong Eun
authors.initials: KE
authors.lastname: Hyung
authors.forename: Mi Ji
authors.initials: MJ
authors.lastname: Lee
authors.forename: Young-hye
authors.initials: YH
authors.lastname: Moon
authors.forename: Ik Hee
authors.initials: IH
authors.lastname: Lee
authors.forename: Byung Sung
authors.initials: BS
authors.lastname: Go
authors.forename: So-Young
authors.initials: SY
authors.lastname: Park
authors.forename: Kwang Woo
authors.initials: KW
authors.lastname: Hwang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D016923:Cell Death / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C494812:Bcl2l1 protein, mouse; C000606776:Bcl2l11 protein, mouse; D016207:Cytokines; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C489936:Prrx1 protein, mouse; D051020:bcl-X Protein; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II