Hypoxia stimulates endothelial cell angiotensin-converting enzyme antigen synthesis.

Academic Article

Abstract

  • Previous studies from our laboratory indicate that exposure of the rat to chronic normobaric hypoxia reduces stores of active angiotensin-converting enzyme (ACE) in the lung. This study assesses directly the effects of hypoxia on ACE synthesis in cultured porcine pulmonary artery endothelial cells. Confluent cultures were exposed to hypoxia [2.5% O2 at 1 atmosphere (atm)] in a triple gas incubator; controls were cultured in normoxic conditions. After 24-, 48-, and 72-h exposure to hypoxic or normoxic conditions, followed by incubation with [35S]methionine for an additional 24 h under the same conditions, newly synthesized radiolabeled ACE was quantitated. Radiolabeled ACE was isolated by an immunobead procedure using either anti-ACE (porcine lung) immunoglobin G (IgG) or nonimmune IgG. A single radiolabeled peak (150 kDa) with the same electrophoretic mobility as purified porcine lung ACE was observed. There was a significant time-dependent increase in endothelial cell ACE antigen synthesis without a concomitant change in either cell number or total trichloroacetic (TCA)-precipitable protein in hypoxic cells compared with normoxic controls. In contrast, ACE activity, assessed by conversion of 125I-labeled angiotensin I to 125I-labeled angiotensin II was unchanged in cultures exposed to hypoxia (2.5% O2). This suggests that an inactive form of ACE is synthesized by cultured pulmonary artery endothelial cells under hypoxic conditions.
  • Authors

    Published In

    Keywords

  • Anaerobiosis, Animals, Antigen-Antibody Complex, Cells, Cultured, Endothelium, Vascular, Hypoxia, Immunoglobulin G, Molecular Weight, Peptidyl-Dipeptidase A, Pulmonary Artery
  • Digital Object Identifier (doi)

    Author List

  • King SJ; Booyse FM; Lin PH; Traylor M; Narkates AJ; Oparil S
  • Start Page

  • C1231
  • End Page

  • C1238
  • Volume

  • 256
  • Issue

  • 6 Pt 1