The protective effect of imatinib against pancreatic ß-cell apoptosis induced by dexamethasone via increased GSTP1 expression and reduced oxidative stress.
Sci Rep
; 14(1): 17691, 2024 07 31.
Article
em En
| MEDLINE
| ID: mdl-39085384
ABSTRACT
Glucocorticoids (GCs) are known to stimulate pancreatic beta (ß)-cell apoptosis via several mechanisms, including oxidative stress. Our previous study suggested an increase in dexamethasone-induced pancreatic ß-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 ß-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 ß-cell apoptosis induced by dexamethasone. In conclusion, imatinib decreases pancreatic ß-cell apoptosis induced by dexamethasone via increased GSTP1 expression and reduced oxidative stress.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dexametasona
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Apoptose
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Estresse Oxidativo
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Células Secretoras de Insulina
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Glutationa S-Transferase pi
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Mesilato de Imatinib
Limite:
Animals
Idioma:
En
Revista:
Sci Rep
/
Sci. rep. (Nat. Publ. Group)
/
Scientific reports (Nature Publishing Group)
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Tailândia