Su Y, Block E R
Department of Medicine, University of Florida College of Medicine, Gainesville, USA.
Am J Physiol. 1997 May;272(5 Pt 1):L934-8. doi: 10.1152/ajplung.1997.272.5.L934.
Pulmonary artery endothelial cells (PAEC) possess a two-step pathway for synthesizing L-arginine from L-citrulline. The first and rate-limiting step is catalyzed by argininosuccinate synthetase (AS). We have previously shown that hypoxia inhibits synthesis of L-arginine from L-citrulline in PAEC. In this study, we examined the effect of hypoxia on the induction of AS in PAEC. Porcine PAEC were incubated with or without endotoxin under normoxia (air-5% CO2) or hypoxia (0% O2-95% N2-5% CO2) for 24 h, and then AS activity and AS mRNA content were determined. Incubation with endotoxin resulted in increases in AS activity and mRNA, and the latter was blocked by actinomycin D. Exposure to hypoxia for 24 h decreased AS activity and mRNA content and stability, and it also abolished the increases in AS activity and mRNA induced by endotoxin. These results indicate that hypoxia inhibits endotoxin-mediated induction of AS. This inhibition might reduce the availability of intracellular L-arginine and thereby limit immunostimulant-induced nitric oxide production by lung endothelial cells.
肺动脉内皮细胞（PAEC）具有从L-瓜氨酸合成L-精氨酸的两步途径。第一步也是限速步骤由精氨琥珀酸合成酶（AS）催化。我们之前已经表明，缺氧会抑制PAEC中从L-瓜氨酸合成L-精氨酸的过程。在本研究中，我们研究了缺氧对PAEC中AS诱导的影响。将猪PAEC在常氧（空气-5%二氧化碳）或缺氧（0%氧气-95%氮气-5%二氧化碳）条件下与内毒素一起或不与内毒素一起孵育24小时，然后测定AS活性和AS mRNA含量。与内毒素一起孵育导致AS活性和mRNA增加，而后者被放线菌素D阻断。暴露于缺氧24小时会降低AS活性、mRNA含量和稳定性，并且还消除了内毒素诱导的AS活性和mRNA增加。这些结果表明，缺氧会抑制内毒素介导的AS诱导。这种抑制可能会减少细胞内L-精氨酸的可用性，从而限制免疫刺激剂诱导的肺内皮细胞一氧化氮产生。
