Kolodecik T R, Aten R F, Behrman H R
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06520-8063, USA.
Biochem Pharmacol. 1998 May 1;55(9):1497-503. doi: 10.1016/s0006-2952(97)00668-0.
Luteal cells contain high levels of ascorbic acid that is secreted by stimulation with agents like luteinizing hormone (LH) and prostaglandin F2 alpha (PGF2 alpha). One role for interstitial ascorbic acid, we propose, may be the detoxification of H2O2 by regeneration of catalytically active peroxidase. By serving as a preferred secondary substrate, ascorbic acid regenerates the catalytically active peroxidase that is inhibited irreversibly by H2O2 alone. To test this hypothesis, luteal cells were incubated in the absence and presence of peroxidases and H2O2, and the maximal cyclic AMP and steroidogenic response to LH was examined. In luteal cells, H2O2 is known to severely inhibit LH-sensitive cyclic AMP accumulation and steroidogenesis, and the addition of lactoperoxidase, myeloperoxidase, eosinophil peroxidase, or ascorbic acid (1 mM) alone had no effect on these responses to H2O2. However, co-incubation of ascorbic acid and the peroxidases completely reversed the inhibition of cyclic AMP accumulation and steroidogenesis produced by H2O2. These findings and the results that show direct oxidation of ascorbic acid in the presence of peroxidase and H2O2, but not with H2O2 alone, support the conclusion that ascorbic acid released from cells may detoxify H2O2 by regenerating the catalytically active state of peroxidases.
黄体细胞含有高水平的抗坏血酸，这种抗坏血酸是由促黄体生成素（LH）和前列腺素F2α（PGF2α）等物质刺激分泌的。我们提出，间质抗坏血酸的一个作用可能是通过再生具有催化活性的过氧化物酶来对过氧化氢进行解毒。作为一种优先的二级底物，抗坏血酸能使被单独的过氧化氢不可逆抑制的具有催化活性的过氧化物酶再生。为了验证这一假设，将黄体细胞分别在不存在和存在过氧化物酶及过氧化氢的情况下进行孵育，并检测对促黄体生成素的最大环磷酸腺苷和类固醇生成反应。在黄体细胞中，已知过氧化氢会严重抑制促黄体生成素敏感的环磷酸腺苷积累和类固醇生成，单独添加乳过氧化物酶、髓过氧化物酶、嗜酸性粒细胞过氧化物酶或抗坏血酸（1 mM）对这些过氧化氢反应没有影响。然而，抗坏血酸与过氧化物酶共同孵育完全逆转了过氧化氢对环磷酸腺苷积累和类固醇生成的抑制作用。这些发现以及表明在过氧化物酶和过氧化氢存在下抗坏血酸直接氧化，但单独与过氧化氢不存在这种情况的结果，支持了从细胞中释放的抗坏血酸可能通过再生过氧化物酶的催化活性状态来对过氧化氢进行解毒的结论。
