Insulin modulates induction of glucose-regulated protein 78 during endoplasmic reticulum stress via augmentation of ATF4 expression in human neuroblastoma cells

Kiyoshi Inageda

doi:10.1016/j.febslet.2010.07.040

Insulin modulates induction of glucose-regulated protein 78 during endoplasmic reticulum stress via augmentation of ATF4 expression in human neuroblastoma cells

FEBS Lett. 2010 Aug 20;584(16):3649-54. doi: 10.1016/j.febslet.2010.07.040. Epub 2010 Jul 25.

Author

Kiyoshi Inageda¹

Affiliation

¹ Department of Hygiene and Public Health I, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. inageda@research.twmu.ac.jp

PMID: 20667453
DOI: 10.1016/j.febslet.2010.07.040

Abstract

The effect of insulin on endoplasmic reticulum (ER) stress was investigated. Insulin protected cell death induced by ER stress and increased glucose-regulated protein 78 (GRP78) mRNA and protein levels. Insulin also significantly increased activating transcription factor-4 (ATF4) protein in the nucleus, which was inhibited by LY294002, a phosphatidylinositol 3-kinase (PI-3 kinase) inhibitor. The increase of ATF4 protein by insulin was not due to transcriptional or translational up-regulation but to a post-translational mechanism. Knockdown of ATF4 by siRNA significantly inhibited GRP78 induction by insulin. These results indicate that insulin modulated ER stress-induced GRP78 expression occurs via ATF4 up-regulation.

MeSH terms

Activating Transcription Factor 4 / antagonists & inhibitors
Activating Transcription Factor 4 / genetics
Activating Transcription Factor 4 / metabolism*
Base Sequence
Caspase 3 / metabolism
Cell Death / drug effects
Cell Line, Tumor
Chromones / pharmacology
DNA Primers / genetics
Endoplasmic Reticulum / drug effects*
Endoplasmic Reticulum / metabolism*
Endoplasmic Reticulum Chaperone BiP
Enzyme Activation / drug effects
Gene Knockdown Techniques
Heat-Shock Proteins / biosynthesis*
Heat-Shock Proteins / genetics
Humans
Insulin / pharmacology*
Morpholines / pharmacology
Neuroblastoma / metabolism*
Phosphoinositide-3 Kinase Inhibitors
Protein Processing, Post-Translational / drug effects
Protein Stability / drug effects
RNA, Small Interfering / genetics
Stress, Physiological
Up-Regulation / drug effects

Substances

ATF4 protein, human
Chromones
DNA Primers
Endoplasmic Reticulum Chaperone BiP
HSPA5 protein, human
Heat-Shock Proteins
Insulin
Morpholines
Phosphoinositide-3 Kinase Inhibitors
RNA, Small Interfering
Activating Transcription Factor 4
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
CASP3 protein, human
Caspase 3