Inhibition of pulmonary artery smooth muscle cell growth by hypoxanthine, xanthine, and uric acid.
Inhibition of pulmonary artery smooth muscle cell growth by hypoxanthine, xanthine, and uric acid.
复制标题
次黄嘌呤、黄嘌呤和尿酸抑制肺动脉平滑肌细胞生长。
DOI：
10.1165/ajrcmb/6.6.617
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发表时间：
1992
影响因子：
6.4
通讯作者：
Fanburg,BL
中科院分区：
文献类型：
--
作者：
Hassoun,PM;Shedd,AL;Lanzillo,JJ;Thappa,V;Landman,MJ;Fanburg,BL
我们以前曾报道，缺氧肺动脉内皮细胞（ECCM）的条件培养基中含有一个小分子量的因子，抑制肺动脉平滑肌细胞（SMC）的生长。我们推测，这一因素可能是ATP的分解产物，因此，测定了次黄嘌呤/黄嘌呤（HX/X）和尿酸（UA）的ECCM和细胞裂解物暴露于缺氧和常氧的内皮细胞（EC）的水平。虽然缺氧和常氧细胞裂解液不含UA和等量的HX/X，（分别为2.9 ± 0.3和2.9 ± 0.5μM），与常氧ECCM相比，低氧ECCM中存在的HX/X量增加了5倍（分别为3.4 ±0.3和0.6 ± 0.4µM;P< 0.001），但UA水平无差异（分别为5 ± 2和5 ± 1µM）。在单独的实验中，我们检查了外源性HX、X和UA（剂量范围为0.1至100µM）对肺和主动脉SMC以及肺动脉EC增殖的影响。我们的结果表明，HX，X和UA抑制SMC增殖的剂量依赖性的方式，而不造成细胞损伤。另一方面，EC的增殖不受UA的影响，并且仅在100µM剂量下被HX和X显著抑制。总之，我们已经发现，显着量的HX/X积累在缺氧ECCM和HX，X和UA抑制SMC的增殖。这些研究结果的相关性缺氧盛行的条件进行了讨论。
We have previously reported that medium conditioned by hypoxic pulmonary artery endothelial cells (ECCM) contains a factor of small molecular weight that inhibits the growth of pulmonary artery smooth muscle cells (SMC). We postulated that this factor might be a breakdown product of ATP and, therefore, measured the levels of hypoxanthine/xanthine (HX/X) and uric acid (UA) in ECCM and cell lysates from endothelial cells (EC) exposed to hypoxia and normoxia. Although hypoxic and normoxic cell lysates contained no UA and an equal amount of HX/X (2.9 ± 0.3 and 2.9 ± 0.5µM, respectively), there was a 5-fold increase in the amount of HX/X present in hypoxic compared with normoxic ECCM (3.4 ±0.3 versus 0.6 ± 0.4µM, respectively;P< 0.001) but no difference in UA levels (5 ± 2 versus 5 ± 1µM, respectively). In separate experiments, we examined the effects of exogenous HX, X, and UA (doses ranging from 0.1 to 100µM) on the proliferation of pulmonary and aortic SMC and pulmonary artery EC. Our results indicate that HX, X, and UA inhibit the proliferation of SMC in a dose-dependent manner without causing injury to the cells. The proliferation of EC, on the other hand, was not affected by UA and was significantly inhibited by HX and X only at doses of 100µM. In conclusion, we have found that significant amounts of HX/X accumulate in hypoxic ECCM and that HX, X, and UA inhibit the proliferation of SMC. The relevance of these findings to conditions where hypoxia prevails is discussed.