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PMID: 18723000 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Akt kinase reducing endoplasmic reticulum Ca2+ release protects cells from Ca2+-dependent apoptotic stimuli.

Biochemical and biophysical research communications ·Vol. 375 ·No. 4 ·2008-10-31 ·Pages 501-5

Marchi S, Rimessi A, Giorgi C, Baldini C, Ferroni L, Rizzuto R, Pinton P

Abstract

The proto-oncogene Akt is a potent inhibitor of apoptosis, and it is activated in many human cancers. A number of recent studies have highlighted the importance of the inositol 1,4,5-trisphosphate (IP3) receptor(IP3R) in mediating calcium (Ca2+) transfer from the endoplasmic reticulum (ER) to the mitochondriain several models of apoptosis. Akt is a serine-threonine kinase and recent data indicate the IP3R as a target of its phosphorylation activity. Here we show that HeLa cells, overexpressing the constitutively active myristoylated/palmitylatedAKT1 (m/p-AKT1), were found to have a reduced Ca2+ release from ER after stimulation with agonist coupled to the generation of IP3. In turn, this affected cytosolic and mitochondria Ca2+ response after Ca2+release from the ER induced either by agonist stimulation or by apoptotic stimuli releasing Ca2+ from intracellular stores. Most importantly, this alteration of ER Ca2+ content and release, reduces significantly cellular sensitivity to Ca2+ mediated proapoptotic stimulation. These results reveal a primary role of Akt in shaping intracellular Ca2+ homeostasis, that may underlie its protective role against some proapoptotic stimuli.

MeSH Terms
Apoptosis Arachidonic Acid/pharmacology Calcium/metabolism Cytosol/metabolism Endoplasmic Reticulum/metabolism HeLa Cells Humans Hydrogen Peroxide/pharmacology Inositol 1,4,5-Trisphosphate Receptors/metabolism Mitochondria/metabolism Proto-Oncogene Mas Proto-Oncogene Proteins c-akt/genetics,metabolism
Chemicals
Inositol 1,4,5-Trisphosphate Receptors MAS1 protein, human Proto-Oncogene Mas Arachidonic Acid Hydrogen Peroxide Proto-Oncogene Proteins c-akt Calcium
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Marchi Saverio
Department of Experimental and Diagnostic Medicine, Section of General Pathology, Interdisciplinary Center for the Study of Inflammation (ICSI), University of Ferrara, Via Borsari 46, I-44100 Ferrara, Italy.
Rimessi Alessandro
Giorgi Carlotta
Baldini Claudio
Ferroni Letizia
Rizzuto Rosario
Pinton Paolo
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Article Info
Journal
Biochemical and biophysical research communications
Abbr.
Biochem Biophys Res Commun
ISSN
1090-2104
DOI
10.1016/j.bbrc.2008.07.153
Published
2008-10-31
Epub
2008-00-22
Pages
501-5
Language
English
Region
United States
NLM ID
0372516
PMCID
PMC2576286
Subset
IM
Grants
Telethon · GTF02013 · Italy
NIA NIH HHS · P01 AG025532 · United States
NIA NIH HHS · P01 AG025532-01A16359 · United States
NIA NIH HHS · 1P01AG025532-01A1 · United States
External Links
PubMed source DOI: 10.1016/j.bbrc.2008.07.153 PMC Full Text View journal details
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