Selective inhibition of heme oxygenase, without inhibition of nitric oxide synthase or soluble guanylyl cyclase, by metalloporphyrins at low concentrations.
Selective inhibition of heme oxygenase, without inhibition of nitric oxide synthase or soluble guanylyl cyclase, by metalloporphyrins at low concentrations.
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DOI：
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发表时间：
1999-10
期刊：
影响因子：
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通讯作者：
Scott D. Appleton;Marc L Chretien;B. McLaughlin;H. Vreman;David K. Stevenson;James F. Brien;Kanji Nakatsu;Donald H. Maurice;Gerald S. Marks
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文献类型：
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作者：
Scott D. Appleton;Marc L Chretien;B. McLaughlin;H. Vreman;David K. Stevenson;James F. Brien;Kanji Nakatsu;Donald H. Maurice;Gerald S. Marks
对血红素加氧酶(HO)的生理作用的研究需要一种选择性地抑制HO活性的抑制剂，而不抑制一氧化氮合酶(NOS)或可溶性鸟苷环化酶(SGC)的活性。这项研究的目的是测试一系列以前被证明抑制HO活性的金属卟啉，以了解它们在不抑制NOS或sGC活性的情况下抑制HO的能力。用金属卟啉(0.15-50微米)孵育大鼠脑微粒体中的HO活性和大鼠脑胞浆中的一氧化氮合酶(NOS)。CRMP和ZnBG是HO活性的选择性最高的抑制剂(即对HO活性的抑制最大，和80%，而对一氧化氮合酶活性没有抑制作用)。在此基础上，测定了CRMP或ZnBG(0.15-15微米)孵育大鼠肺细胞胞浆中sGC的活性。锌BG对基础sGC活性无影响，但对S-亚硝基-N-乙酰青霉胺诱导的sGC活性有增强作用。CRMP既不影响基础活动，也不影响SNAP诱导的活动。结果表明，在所研究的五种金属卟啉中，浓度为5微米的CRMP是一种选择性的HO活性抑制剂，在所测试的条件下是最有用的金属卟啉。因此，CRMP在阐明HO的生理作用方面似乎是一个有价值的化学探针。
Studies on the physiological role of heme oxygenase (HO) require an inhibitor that will selectively inhibit HO activity without inhibiting the activity of either nitric oxide synthase (NOS) or soluble guanylyl cyclase (sGC). The objective of this study was to test a series of metalloporphyrins that have previously been shown to inhibit HO activity, for their ability to inhibit HO without inhibiting NOS or sGC activities. Measurement of activity of HO in rat brain microsomes and NOS in rat brain cytosol was made for samples incubated with metalloporphyrins (0.15-50 microM), including zinc protoporphyrin IX, zinc deuteroporphyrin IX 2,4-bis-ethylene glycol (ZnBG), chromium mesoporphyrin IX (CrMP), tin protoporphyrin IX, and zinc N-methylprotoporphyrin IX. CrMP and ZnBG were found to be the most selective inhibitors of HO activity (i.e., caused the greatest inhibition of HO activity, 89 and 80%, respectively, without inhibition of NOS activity). Based on these results, sGC activity in rat lung cytosol incubated with CrMP or ZnBG (0.15-15 microM) was measured. ZnBG did not affect basal sGC activity but did potentiate S-nitroso-N-acetylpenicillamine (SNAP)-induced sGC activity. CrMP did not affect either basal or SNAP-induced activity. It was concluded that of the five metalloporphyrins studied, CrMP, at a concentration of 5 microM, was a selective inhibitor of HO activity and was the most useful metalloporphyrin for the conditions tested. Thus, CrMP would appear to be a valuable chemical probe in elucidating the physiological role of HO.