title: Involvement of Ca2+-mediated apoptotic signals in palmitate-induced MIN6N8a beta cell death.
abstract: The extracellular Ca(2+) chelator EGTA and L-type Ca(2+) channel blockers, such as, nifedipine and nimodipine were found to have a protective effect on palmitate-induced MIN6N8a beta cell apoptosis, whereas the Ca(2+) channel opener, Bay K8644, enhanced the apoptotic process. Moreover, the phospho-form of Bad, in conjunction with phospho-Akt, was reduced in response to palmitate and the palmitate-induced dephosphorylations of Akt and Bad were dependent on Ca(2+) influx. The transient expression of catalytically active Akt prevented MIN6N8a cells from palmitate-induced apoptosis. Deltamethrin, an inhibitor of Ca(2+)-activated phosphatase, delayed Akt and Bad dephosphorylations, and then protected MIN6N8a cells from palmitate-induced apoptosis. On the other hand, palmitate was found to induce CHOP, an apoptotic transcription factor in response to ER stress, and this induction was enhanced by Ca(2+) influx. Our studies suggested that Ca(2+) influx and subsequent Ca(2+)-mediated apoptotic signals are involved in palmitate-induced beta cell death.
authors.affiliation: Institute for Medical Science, Ajou University School of Medicine, 442-749 Suwon, Republic of Korea.
authors.forename: Sung-E
authors.initials: SE
authors.lastname: Choi
authors.forename: Hyo-Eun
authors.initials: HE
authors.lastname: Kim
authors.forename: Ha-Chul
authors.initials: HC
authors.lastname: Shin
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Jang
authors.forename: Kwan-Woo
authors.initials: KW
authors.lastname: Lee
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Sang Sun
authors.initials: SS
authors.lastname: Kang
authors.forename: Jaesun
authors.initials: J
authors.lastname: Chun
authors.forename: Yup
authors.initials: Y
authors.lastname: Kang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019703:Calcineurin / Q000502:physiology; D002118:Calcium / Q000037:antagonists & inhibitors / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D002614:Chelating Agents; D020011:Protective Agents; D051025:bcl-Associated Death Protein; D019308:Palmitic Acid; D051058:Oncogene Protein v-akt; D019703:Calcineurin; D002118:Calcium