Upregulation of caveolin-1 and its colocalization with cytokine receptors contributes to beta cell apoptosis

• Published in: Scientific reports 2019-11, Vol.9 (1), p.16785-10, Article 16785
• Main Authors: Bae, Gong Deuk, Park, Eun-Young, Kim, Kyong, Jang, Se-Eun, Jun, Hee-Sook, Oh, Yoon Sin
• Format: Article
• Language: English
• Subjects: 13/1; 13/2; 38/89; 45/90; 631/337/505; 631/45/127; 82/29; 96/109; Animals; Apoptosis; Beta cells; Caveolae; Caveolae - metabolism; Caveolin; Caveolin 1 - antagonists & inhibitors; Caveolin 1 - genetics; Caveolin 1 - metabolism; Caveolin-1; Cell death; Cell Survival - drug effects; Cell viability; Cells, Cultured; Cytokine receptors; Cytokines; Cytokines - pharmacology; Diabetes mellitus (non-insulin dependent); Gene expression; Humanities and Social Sciences; IL-1β; Insulin-Secreting Cells - cytology; Interleukin 1; Interleukin 1 receptors; Interleukin-1beta - pharmacology; Lipid rafts; multidisciplinary; NF-κB protein; Nitric-oxide synthase; Rats; Receptors, Cytokine - metabolism; RNA, Small Interfering - pharmacology; Science; Science (multidisciplinary); siRNA; Transfection; Tumor necrosis factor receptors; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-α; Up-Regulation - drug effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-53278-z

Caveolin-1 (cav-1), the principal structural and signalling protein of caveolae, is implicated in various signalling events, including apoptotic cell death in type 2 diabetes. However, the precise role of beta cells in apoptosis has not been clearly defined. In this study, we investigated the involvement of cav-1 in cytokine-induced beta cell apoptosis and its underlying mechanisms in the rat beta cell line, INS-1 and isolated islets. Treatment of cytokine mixture (CM, TNFα + IL-1β) significantly increased the mRNA and protein expression of cav-1, and resulting in increased formation of caveolae. We found that IL-1 receptor 1 and TNF receptor localized to plasma membrane lipid rafts in the control cells and CM treatment recruited these receptors to the caveolae domain. After cav-1 siRNA transfection, CM-dependent NF-κB activation was reduced and consequently downregulated the mRNA expression of iNOS and IL-1β. Finally, decreased cell viability by CM treatment was ameliorated in both INS-1 cells and isolated islets treated with cav-1 siRNA. These results suggest that increased cav-1 expression and recruitment of cytokine receptors into caveolae contribute to CM-induced beta cell apoptosis.