Hypoxic stimulation of the stress-activated protein kinases in pulmonary artery fibroblasts

Scott, P. H., Paul, A., BElham, C. M., Peacock, A. J., Wadsworth, R. M., Gould, G. W., Welsh, D. and Plevin, R. (1998) Hypoxic stimulation of the stress-activated protein kinases in pulmonary artery fibroblasts. American Journal of Respiratory and Critical Care Medicine, 158(3), pp. 958-962. (doi: 10.1164/ajrccm.158.3.9712130) (PMID:9731031)

Abstract

Pulmonary hypertension in response to chronic hypoxia is invariably accompanied by remodeling of the pulmonary vessels but the mechanism by which hypoxia increases the replication of vascular cells is unknown. To investigate the hypothesis that hypoxia stimulates intracellular kinase cascades we measured the activity of “classic” mitogen-activated protein (MAP) kinase pathways and “stress- activated” MAP kinase pathways in bovine pulmonary artery fibroblasts subjected to hypoxia for up to 30 h. Hypoxia (1% O2) stimulated strongly the stress-activated protein kinases, c-Jun NH2-terminal kinase (JNK) and p38 MAP kinase. Two peaks of p38 MAP kinase activity at 6 and 24 h were associated with an increase in the activity of mitogen-activated protein kinase-activated protein (MAPKAP) kinase-2, the immediate downstream target of p38 MAP kinase. Furthermore, the second phase of p38 MAP kinase activity could be reversed if cells were reoxygenated after 12 h. These data suggest that hypoxic stimulation of pulmonary artery cells is mediated by activation of the stress-activated protein kinases.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Scott, Dr Pamela
• Authors: Scott, P. H., Paul, A., BElham, C. M., Peacock, A. J., Wadsworth, R. M., Gould, G. W., Welsh, D., and Plevin, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences
• Journal Name: American Journal of Respiratory and Critical Care Medicine
• Publisher: American Thoracic Society
• ISSN: 1073-449X
• ISSN (Online): 1535-4970