Involvement of Ca2+-mediated apoptotic signals in palmitate-induced MIN6N8a beta cell death.
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.
Choi
Sung-E
SE
Institute for Medical Science, Ajou University School of Medicine, 442-749 Suwon, Republic of Korea.
Kim
Hyo-Eun
HE
Shin
Ha-Chul
HC
Jang
Hyun-Ju
HJ
Lee
Kwan-Woo
KW
Kim
Youngsoo
Y
Kang
Sang Sun
SS
Chun
Jaesun
J
Kang
Yup
Y
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
D002614:Chelating Agents; D020011:Protective Agents; D051025:bcl-Associated Death Protein; D019308:Palmitic Acid; D051058:Oncogene Protein v-akt; D019703:Calcineurin; D002118:Calcium