The protective effect of imatinib against pancreatic β-cell apoptosis induced by dexamethasone via increased GSTP1 expression and reduced oxidative stress
Issued Date
2024-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85200214478
Journal Title
Scientific Reports
Volume
14
Issue
1
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SCOPUS
Bibliographic Citation
Scientific Reports Vol.14 No.1 (2024)
Suggested Citation
Semprasert N., Maneethorn P., Kooptiwut S. The protective effect of imatinib against pancreatic β-cell apoptosis induced by dexamethasone via increased GSTP1 expression and reduced oxidative stress. Scientific Reports Vol.14 No.1 (2024). doi:10.1038/s41598-024-68429-0 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/100388
Title
The protective effect of imatinib against pancreatic β-cell apoptosis induced by dexamethasone via increased GSTP1 expression and reduced oxidative stress
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Abstract
Glucocorticoids (GCs) are known to stimulate pancreatic beta (β)-cell apoptosis via several mechanisms, including oxidative stress. Our previous study suggested an increase in dexamethasone-induced pancreatic β-cell apoptosis via a reduction of glutathione S-transferase P1 (GSTP1), which is an antioxidant enzyme. Imatinib, which is a tyrosine kinase inhibitor, also exerts antioxidant effect. This study aims to test our hypothesis that imatinib would prevent pancreatic β-cell apoptosis induced by dexamethasone via increased GSTP1 expression and reduced oxidative stress. Our results revealed that dexamethasone significantly increased apoptosis in INS-1 cells when compared to the control, and that imatinib significantly decreased INS-1 cell apoptosis induced by dexamethasone. Moreover, dexamethasone significantly increased superoxide production in INS-1 cells when compared to the control; however, imatinib, when combined with dexamethasone, significantly reduced superoxide production in INS-1 cells. Dexamethasone significantly decreased GSTP1, p-ERK1/2, and BCL2 protein expression, but significantly increased p-JNK, p-p38, and BAX protein expression in INS-1 cells—all compared to control. Importantly, imatinib significantly ameliorated the effect of dexamethasone on the expression of GSTP1, p-ERK1/2, p-JNK, p-p38 MAPK, BAX, and BCL2. Furthermore—6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX), which is a GSTP1 inhibitor, neutralized the protective effect of imatinib against pancreatic β-cell apoptosis induced by dexamethasone. In conclusion, imatinib decreases pancreatic β-cell apoptosis induced by dexamethasone via increased GSTP1 expression and reduced oxidative stress.