DC Field | Value | Language |
---|---|---|
dc.contributor.author | Tuyet Thi Nguyen | ko |
dc.contributor.author | Quan, Xianglan | ko |
dc.contributor.author | Xu, Shanhua | ko |
dc.contributor.author | Das, Ranjan | ko |
dc.contributor.author | Cha, Seung-Kuy | ko |
dc.contributor.author | Kong, In Deok | ko |
dc.contributor.author | Shong, Minho | ko |
dc.contributor.author | Wollheim, Claes B. | ko |
dc.contributor.author | Park, Kyu-Sang | ko |
dc.date.accessioned | 2023-04-12T06:00:48Z | - |
dc.date.available | 2023-04-12T06:00:48Z | - |
dc.date.created | 2023-04-12 | - |
dc.date.created | 2023-04-12 | - |
dc.date.issued | 2016-12 | - |
dc.identifier.citation | FASEB JOURNAL, v.30, no.12, pp.3979 - 3988 | - |
dc.identifier.issn | 0892-6638 | - |
dc.identifier.uri | http://hdl.handle.net/10203/306135 | - |
dc.description.abstract | Elevated plasma levels of inorganic phosphate (Pi) are harmful, causing, among other complications, vascular calcification and defective insulin secretion. The underlying molecular mechanisms of these complications remain poorly understood. We demonstrated the role of Pi transport across the plasmalemma on Pi toxicity in INS-1E rat clonal beta cells and rat pancreatic islet cells. Type III sodium-phosphate cotransporters (NaP(i)s) are the predominant P-i transporters expressed in insulin-secreting cells. Transcript and protein levels of sodium-dependent phosphate transporter 1 and 2 (PiT-1and -2), isotypes of type III NaPi, were up-regulated by high-Pi incubation. In patch-clamp experiments, extracellular P-i elicited a Na+-dependent, inwardly rectifying current, which was markedly reduced under acidic extracellular conditions. Cellular uptake of P-i elicited cytosolic alkalinization; intriguingly, this pH change facilitated P-i transport into the mitochondrial matrix. Increased mitochondrial P-i uptake accelerated superoxide generation, mitochondrial permeability transition (mPT), and endoplasmic reticulum stress-mediated translational attenuation, leading to reduced insulin content and impaired glucose-stimulated insulin secretion. Silencing of PiT-1/2 prevented Pi-induced superoxide generation and mPT, and restored insulin secretion. We propose that P-i transport across the plasma membrane and consequent cytosolic alkalinization could be a therapeutic target for protection from P-i toxicity in insulin-secreting cells, as well as in other cell types.-Nguyen, T. T., Quan, X., Xu, S., Das, R., Cha, S.-K., Kong, I. D., Shong, M., Wollheim, C. B., Park, K.-S. Intracellular alkalinization by phosphate uptake via type III sodium-phosphate cotransporter participates in high-phosphate-induced mitochondrial oxidative stress and defective insulin secretion. | - |
dc.language | English | - |
dc.publisher | FEDERATION AMER SOC EXP BIOL | - |
dc.title | Intracellular alkalinization by phosphate uptake via type III sodium-phosphate cotransporter participates in high-phosphate-induced mitochondrial oxidative stress and defective insulin secretion | - |
dc.type | Article | - |
dc.identifier.wosid | 000388201500006 | - |
dc.identifier.scopusid | 2-s2.0-85002050591 | - |
dc.type.rims | ART | - |
dc.citation.volume | 30 | - |
dc.citation.issue | 12 | - |
dc.citation.beginningpage | 3979 | - |
dc.citation.endingpage | 3988 | - |
dc.citation.publicationname | FASEB JOURNAL | - |
dc.identifier.doi | 10.1096/fj.201600455RR | - |
dc.contributor.localauthor | Shong, Minho | - |
dc.contributor.nonIdAuthor | Tuyet Thi Nguyen | - |
dc.contributor.nonIdAuthor | Quan, Xianglan | - |
dc.contributor.nonIdAuthor | Xu, Shanhua | - |
dc.contributor.nonIdAuthor | Das, Ranjan | - |
dc.contributor.nonIdAuthor | Cha, Seung-Kuy | - |
dc.contributor.nonIdAuthor | Kong, In Deok | - |
dc.contributor.nonIdAuthor | Wollheim, Claes B. | - |
dc.contributor.nonIdAuthor | Park, Kyu-Sang | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | inorganic phosphate | - |
dc.subject.keywordAuthor | pancreatic beta cells | - |
dc.subject.keywordAuthor | mitochondrial permeability transition | - |
dc.subject.keywordAuthor | endoplasmic reticulum stress | - |
dc.subject.keywordAuthor | superoxide | - |
dc.subject.keywordPlus | PERMEABILITY TRANSITION PORE | - |
dc.subject.keywordPlus | INORGANIC-PHOSPHATE | - |
dc.subject.keywordPlus | BETA-CELLS | - |
dc.subject.keywordPlus | KLOTHO | - |
dc.subject.keywordPlus | CALCIFICATION | - |
dc.subject.keywordPlus | STIMULATION | - |
dc.subject.keywordPlus | METABOLISM | - |
dc.subject.keywordPlus | FLUORESCENCE | - |
dc.subject.keywordPlus | HOMEOSTASIS | - |
dc.subject.keywordPlus | GENERATION | - |
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