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IGF-1 regulates cardiac fibroblast apoptosis induced by osmotic stress.
Biochem Biophys Res Commun. 2000 Jun 24; 273(1):322-7.BB

Abstract

In this study we have determined the ability of IGF-1 to protect cardiac fibroblasts against osmotic-induced apoptosis and investigated the potential mechanism(s) underlying this protection. Treatment with IGF-1 (1-100 ng/ml) promoted a dose dependent increase in cell survival against osmotic cell death. Both Akt and ERK1/2 were rapidly phosphorylated by IGF-1 and blocked by wortmannin and PD98059, inhibitors of their upstream activators respectively. However, IGF-1-induced protection was mediated via a wortmannin-dependent but PD98059-independent pathway as determined by cell survival assay suggesting a role of PI3-K/Akt. Furthermore, IGF-1 appeared to reduce the activation of a number of early components in the apoptotic pathway in a wortmannin dependent manner including the osmotic stress-induced perturbation in mitochondrial membrane potential, cleavage and activation of caspase-3 and DNA fragmentation. Thus, the results suggest that IGF-1 regulates osmotic stress-induced apoptosis via the activation of the PI3-K/Akt pathway at a point upstream of the mitochondria and caspase-3.

Authors+Show Affiliations

Department of Cardiology, St. Thomas' Hospital, London, SE1 7EH, United Kingdom. james.mockridge@kcl.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10873605

Citation

Mockridge, J W., et al. "IGF-1 Regulates Cardiac Fibroblast Apoptosis Induced By Osmotic Stress." Biochemical and Biophysical Research Communications, vol. 273, no. 1, 2000, pp. 322-7.
Mockridge JW, Benton EC, Andreeva LV, et al. IGF-1 regulates cardiac fibroblast apoptosis induced by osmotic stress. Biochem Biophys Res Commun. 2000;273(1):322-7.
Mockridge, J. W., Benton, E. C., Andreeva, L. V., Latchman, D. S., Marber, M. S., & Heads, R. J. (2000). IGF-1 regulates cardiac fibroblast apoptosis induced by osmotic stress. Biochemical and Biophysical Research Communications, 273(1), 322-7.
Mockridge JW, et al. IGF-1 Regulates Cardiac Fibroblast Apoptosis Induced By Osmotic Stress. Biochem Biophys Res Commun. 2000 Jun 24;273(1):322-7. PubMed PMID: 10873605.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IGF-1 regulates cardiac fibroblast apoptosis induced by osmotic stress. AU - Mockridge,J W, AU - Benton,E C, AU - Andreeva,L V, AU - Latchman,D S, AU - Marber,M S, AU - Heads,R J, PY - 2000/6/30/pubmed PY - 2000/6/30/medline PY - 2000/6/30/entrez SP - 322 EP - 7 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 273 IS - 1 N2 - In this study we have determined the ability of IGF-1 to protect cardiac fibroblasts against osmotic-induced apoptosis and investigated the potential mechanism(s) underlying this protection. Treatment with IGF-1 (1-100 ng/ml) promoted a dose dependent increase in cell survival against osmotic cell death. Both Akt and ERK1/2 were rapidly phosphorylated by IGF-1 and blocked by wortmannin and PD98059, inhibitors of their upstream activators respectively. However, IGF-1-induced protection was mediated via a wortmannin-dependent but PD98059-independent pathway as determined by cell survival assay suggesting a role of PI3-K/Akt. Furthermore, IGF-1 appeared to reduce the activation of a number of early components in the apoptotic pathway in a wortmannin dependent manner including the osmotic stress-induced perturbation in mitochondrial membrane potential, cleavage and activation of caspase-3 and DNA fragmentation. Thus, the results suggest that IGF-1 regulates osmotic stress-induced apoptosis via the activation of the PI3-K/Akt pathway at a point upstream of the mitochondria and caspase-3. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/10873605/IGF_1_regulates_cardiac_fibroblast_apoptosis_induced_by_osmotic_stress_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(00)92934-6 DB - PRIME DP - Unbound Medicine ER -