Imatinib prevents dexamethasone-induced pancreatic β-cell apoptosis via decreased TRAIL and DR5
Issued Date
2023-01-01
Resource Type
ISSN
07302312
eISSN
10974644
Scopus ID
2-s2.0-85166911691
Journal Title
Journal of Cellular Biochemistry
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Cellular Biochemistry (2023)
Suggested Citation
Kutpruek S., Suksri K., Maneethorn P., Semprasert N., Yenchitsomanus P.t., Kooptiwut S. Imatinib prevents dexamethasone-induced pancreatic β-cell apoptosis via decreased TRAIL and DR5. Journal of Cellular Biochemistry (2023). doi:10.1002/jcb.30450 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/88368
Title
Imatinib prevents dexamethasone-induced pancreatic β-cell apoptosis via decreased TRAIL and DR5
Author's Affiliation
Other Contributor(s)
Abstract
Prolonged administration of dexamethasone, a potent anti-inflammatory drug, can lead to steroid-induced diabetes. Imatinib, a medication commonly prescribed for chronic myeloid leukemia (CML), has been shown to improve diabetes in CML patients. Our recent study demonstrated that dexamethasone induces pancreatic β-cell apoptosis by upregulating the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor, death receptor 5 (DR5). We hypothesized that imatinib may protect against dexamethasone-induced pancreatic β-cell apoptosis by reducing the expression of TRAIL and DR5, thereby favorably modulating downstream effectors in apoptotic pathways. We test this hypothesis by assessing the effects of imatinib on dexamethasone-induced apoptosis in rat insulinoma cell line cells. As anticipated, dexamethasone treatment led to increased TRAIL and DR5 expression, as well as an elevation in superoxide production. Conversely, expression of the TRAIL decoy receptor (DcR1) was decreased. Moreover, key effectors in the extrinsic and intrinsic apoptosis pathways, such as B-cell lymphoma 2 (BCL-2) associated X (BAX), nuclear factor kappa B (NF-κb), P73, caspase 8, and caspase 9, were upregulated, while the antiapoptotic protein BCL-2 was downregulated. Interestingly and importantly, imatinib at a concentration of 10 µM reversed the effect of dexamethasone on TRAIL, DR5, DcR1, superoxide production, BAX, BCL-2, NF-κB, P73, caspase 3, caspase 8, and caspase 9. Similar effects of imatinib on dexamethasone-induced TRAIL and DR5 expression were also observed in isolated mouse islets. Taken together, our findings suggest that imatinib protects against dexamethasone-induced pancreatic β-cell apoptosis by reducing TRAIL and DR5 expression and modulating downstream effectors in the extrinsic and intrinsic apoptosis pathways.