Involvement of protein kinase C epsilon in the survival effects of insulin-like growth factor-1

Richard T. Allen, Devendra K. Agrawal

Research output: Contribution to journalArticle

Abstract

Insulin-like growth factor-1 (IGF-1), elevated in response to injury, may play a pivotal role during lesion formation in atherosclerosis and post-angioplasty restenosis. We examined the effects of IGF-1 on human aortic SMC apoptosis using Annexin V labeling, ELISA for oligonucleosomes and electron microscopy. We also examined the expression of PKC isozymes by immunoblotting. We show that whereas serum withdrawal induced up to 2% apoptosis, the broad-spectrum PKC inhibitor staurosporine (STAU) induced up to 62% apoptosis. IGF-1 incompletely attenuated apoptosis in a dose-dependent manner, with a max effect occurring between 10-50ng/ml. In addition, human ASMCs express alpha, beta1, delta, epsilon and zeta PKC isozymes and IGF-1 (100ng/ml) dose-dependently increased PKC epsilon expression. STAU decreased PKC epsilon expression by 15-20 fold with the maximum effect at 24 hours. IGF-1 partially reversed the effect of STAU. Our preliminary data revealed that PKC epsilon antisense oligodeoxynucleotides effectively inhibited expression of this isozyme and partially reversed the IGF-1 induced effect These data suggest that PKC epsilon is important in the survival effects of IGF-1 in VSMCs.

Original languageEnglish
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

Fingerprint

Protein Kinase C-epsilon
somatomedins
protein kinase C
Somatomedins
Survival
Staurosporine
apoptosis
Apoptosis
Isoenzymes
isozymes
Oligodeoxyribonucleotides
Annexin A5
dosage
immunoblotting
atherosclerosis
Angioplasty
Immunoblotting
lesions (animal)
Labeling
Electron microscopy

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Involvement of protein kinase C epsilon in the survival effects of insulin-like growth factor-1. / Allen, Richard T.; Agrawal, Devendra K.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

@article{93621f643d8b41b6b108e852e6e1e0f1,
title = "Involvement of protein kinase C epsilon in the survival effects of insulin-like growth factor-1",
abstract = "Insulin-like growth factor-1 (IGF-1), elevated in response to injury, may play a pivotal role during lesion formation in atherosclerosis and post-angioplasty restenosis. We examined the effects of IGF-1 on human aortic SMC apoptosis using Annexin V labeling, ELISA for oligonucleosomes and electron microscopy. We also examined the expression of PKC isozymes by immunoblotting. We show that whereas serum withdrawal induced up to 2{\%} apoptosis, the broad-spectrum PKC inhibitor staurosporine (STAU) induced up to 62{\%} apoptosis. IGF-1 incompletely attenuated apoptosis in a dose-dependent manner, with a max effect occurring between 10-50ng/ml. In addition, human ASMCs express alpha, beta1, delta, epsilon and zeta PKC isozymes and IGF-1 (100ng/ml) dose-dependently increased PKC epsilon expression. STAU decreased PKC epsilon expression by 15-20 fold with the maximum effect at 24 hours. IGF-1 partially reversed the effect of STAU. Our preliminary data revealed that PKC epsilon antisense oligodeoxynucleotides effectively inhibited expression of this isozyme and partially reversed the IGF-1 induced effect These data suggest that PKC epsilon is important in the survival effects of IGF-1 in VSMCs.",
author = "Allen, {Richard T.} and Agrawal, {Devendra K.}",
year = "1998",
month = "3",
day = "20",
language = "English",
volume = "12",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "5",

}

TY - JOUR

T1 - Involvement of protein kinase C epsilon in the survival effects of insulin-like growth factor-1

AU - Allen, Richard T.

AU - Agrawal, Devendra K.

PY - 1998/3/20

Y1 - 1998/3/20

N2 - Insulin-like growth factor-1 (IGF-1), elevated in response to injury, may play a pivotal role during lesion formation in atherosclerosis and post-angioplasty restenosis. We examined the effects of IGF-1 on human aortic SMC apoptosis using Annexin V labeling, ELISA for oligonucleosomes and electron microscopy. We also examined the expression of PKC isozymes by immunoblotting. We show that whereas serum withdrawal induced up to 2% apoptosis, the broad-spectrum PKC inhibitor staurosporine (STAU) induced up to 62% apoptosis. IGF-1 incompletely attenuated apoptosis in a dose-dependent manner, with a max effect occurring between 10-50ng/ml. In addition, human ASMCs express alpha, beta1, delta, epsilon and zeta PKC isozymes and IGF-1 (100ng/ml) dose-dependently increased PKC epsilon expression. STAU decreased PKC epsilon expression by 15-20 fold with the maximum effect at 24 hours. IGF-1 partially reversed the effect of STAU. Our preliminary data revealed that PKC epsilon antisense oligodeoxynucleotides effectively inhibited expression of this isozyme and partially reversed the IGF-1 induced effect These data suggest that PKC epsilon is important in the survival effects of IGF-1 in VSMCs.

AB - Insulin-like growth factor-1 (IGF-1), elevated in response to injury, may play a pivotal role during lesion formation in atherosclerosis and post-angioplasty restenosis. We examined the effects of IGF-1 on human aortic SMC apoptosis using Annexin V labeling, ELISA for oligonucleosomes and electron microscopy. We also examined the expression of PKC isozymes by immunoblotting. We show that whereas serum withdrawal induced up to 2% apoptosis, the broad-spectrum PKC inhibitor staurosporine (STAU) induced up to 62% apoptosis. IGF-1 incompletely attenuated apoptosis in a dose-dependent manner, with a max effect occurring between 10-50ng/ml. In addition, human ASMCs express alpha, beta1, delta, epsilon and zeta PKC isozymes and IGF-1 (100ng/ml) dose-dependently increased PKC epsilon expression. STAU decreased PKC epsilon expression by 15-20 fold with the maximum effect at 24 hours. IGF-1 partially reversed the effect of STAU. Our preliminary data revealed that PKC epsilon antisense oligodeoxynucleotides effectively inhibited expression of this isozyme and partially reversed the IGF-1 induced effect These data suggest that PKC epsilon is important in the survival effects of IGF-1 in VSMCs.

UR - http://www.scopus.com/inward/record.url?scp=33749363018&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749363018&partnerID=8YFLogxK

M3 - Article

VL - 12

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 5

ER -