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

Mol Cell Endocrinol. 2007 Jun 30;272(1-2):50-62. doi: 10.1016/j.mce.2007.04.004. Epub 2007 Apr 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Calcineurin / physiology
  • Calcium / antagonists & inhibitors
  • Calcium / physiology*
  • Cell Death / drug effects
  • Cell Line
  • Chelating Agents / pharmacology
  • Endoplasmic Reticulum / drug effects
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / physiology
  • Male
  • Mice
  • Oncogene Protein v-akt / metabolism
  • Palmitic Acid / pharmacology*
  • Protective Agents / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • bcl-Associated Death Protein / metabolism

Substances

  • Chelating Agents
  • Protective Agents
  • bcl-Associated Death Protein
  • Palmitic Acid
  • Oncogene Protein v-akt
  • Calcineurin
  • Calcium