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Involvement of Ca2+-mediated apoptotic signals in palmitate-induced MIN6N8a beta cell death

Cited 36 time in Web of Science Cited 38 time in Scopus
Authors
Choi, Sung-E; Kim, Hyo-Eun; Shin, Ha-Chul; Jang, Hyun-Ju; Lee, Kwan-Woo; Kim, Youngsoo; Kang, Sang Sun; Chun, Jaesun; Kang, Yup
Issue Date
2007-05-18
Publisher
Elsevier
Citation
Mol Cell Endocrinol. 2007 Jun 30;272(1-2):50-62. Epub 2007 Apr 22.
Keywords
AnimalsApoptosis/*drug effectsCalcineurin/physiologyCalcium/antagonists & inhibitors/*physiologyCell Death/drug effectsCell LineChelating Agents/pharmacologyEndoplasmic Reticulum/drug effectsInsulin-Secreting Cells/*drug effects/physiologyMaleMiceOncogene Protein v-akt/metabolismPalmitic Acid/*pharmacologyProtective Agents/pharmacologyRatsRats, Sprague-DawleySignal Transduction/drug effectsbcl-Associated Death Protein/metabolism
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.
ISSN
0303-7207 (Print)
Language
English
URI
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T3G-4NJG43R-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=3f24636290dffb9e5750e5126026229a

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17507155

http://hdl.handle.net/10371/46604
DOI
https://doi.org/10.1016/j.mce.2007.04.004
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College of Medicine/School of Medicine (의과대학/대학원)Molecular and Genomic Medicine (분자유전체의학전공)Journal Papers (저널논문_분자유전체의학전공)
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