Plant-Produced Asialo-Erythropoietin Restores Pancreatic Beta-Cell Function by Suppressing Mammalian Sterile-20-like Kinase (MST1) and Caspase-3 Activation

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dc.contributor.authorArthur, Elenaen
dc.contributor.authorKittur, Farooqahmed S.en
dc.contributor.authorLin, Yuanen
dc.contributor.authorHung, Chiu-Yuehen
dc.contributor.authorSane, David C.en
dc.contributor.authorXie, Jiahuaen
dc.date.accessioned2019-10-31T14:31:25Zen
dc.date.available2019-10-31T14:31:25Zen
dc.date.issued2017-04-19en
dc.description.abstractPancreatic beta-cell death adversely contributes to the progression of both type I and II diabetes by undermining beta-cell mass and subsequently diminishing endogenous insulin production. Therapeutics to impede or even reverse the apoptosis and dysfunction of beta-cells are urgently needed. Asialo-rhuEPO, an enzymatically desialylated form of recombinant human erythropoietin (rhuEPO), has been shown to have cardioprotective and neuroprotective functions but with no adverse effects like that of sialylated rhuEPO. Heretofore, the anti-apoptotic effect of asialo-rhuEPO on pancreatic beta-cells has not been reported. In the current study, we investigated the cytoprotective properties of plant-produced asialo-rhuEPO (asialo-rhuEPO(P)) against staurosporine-induced cell death in the pancreatic beta-cell line RIN-m5F. Our results showed that 60 IU/ml asialo-rhuEPO(P) provided 41% cytoprotection while 60 IU/ml rhuEPO yielded no effect. Western blotting results showed that asialo-rhuEPO(P) treatment inhibited both MST1 and caspase-3 activation with the retention of PDX1 and insulin levels close to untreated control cells. Our study provides the first evidence indicating that asialo-rhuEPO(P)-mediated protection involves the reduction of MST1 activation, which is considered a key mediator of apoptotic signaling in beta-cells. Considering the many advantages its plant-based expression, asialo-rhuEPO(P) could be potentially developed as a novel and inexpensive agent to treat or prevent diabetes after further performing studies in cell-based and animal models of diabetes.en
dc.description.notesResearch conducted in these studies was supported by National Institute of General Medical Sciences grant (SC1GM111178-01A1) and North Carolina Biotechnology Center Grant (2013-BRG-1207) to JX, and the China Scholarship Council (201408645003) to YL.en
dc.description.sponsorshipNational Institute of General Medical Sciences grantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [SC1GM111178-01A1]; North Carolina Biotechnology Center Grant [2013-BRG-1207]; China Scholarship CouncilChina Scholarship Council [201408645003]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fphar.2017.00208en
dc.identifier.issn1663-9812en
dc.identifier.other208en
dc.identifier.pmid28469576en
dc.identifier.urihttp://hdl.handle.net/10919/95223en
dc.identifier.volume8en
dc.language.isoenen
dc.publisherFrontiersen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectpancreatic beta-cell deathen
dc.subjectinsulin secretionen
dc.subjectMST1en
dc.subjectasialo-rhuEPOen
dc.subjectcytoprotectionen
dc.titlePlant-Produced Asialo-Erythropoietin Restores Pancreatic Beta-Cell Function by Suppressing Mammalian Sterile-20-like Kinase (MST1) and Caspase-3 Activationen
dc.title.serialFrontiers in Pharmacologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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