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

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 involv...

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Bibliographic Details
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:
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
IL-1β
Insulin-Secreting Cells - cytology
Interleukin 1
Interleukin 1 receptors
Interleukin-1beta - pharmacology
Lipid rafts
NF-κB protein
Nitric-oxide synthase
Rats
Receptors, Cytokine - metabolism
RNA, Small Interfering - pharmacology
siRNA
Transfection
Tumor necrosis factor receptors
Tumor Necrosis Factor-alpha - pharmacology
Tumor necrosis factor-α
Up-Regulation - drug effects
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-53278-z