Menon I A, Shirwadkar S, Ranadive N S
Department of Medicine and Ophthalmology, University of Toronto, Ont., Canada.
Biochem Cell Biol. 1989 Aug;67(8):397-403. doi: 10.1139/o89-064.
The present studies were carried out to characterize the nature of reactive oxygen species generated by the xanthine-xanthine oxidase system involved in the release of histamine by noncytotoxic and cytotoxic mechanisms. To distinguish secretory release from lytic release, mast cells were loaded with 51Cr and the release of 51Cr into the incubation medium was used as a measure of cell lysis. The secretory release of histamine was not inhibited by superoxide dismutase or catalase alone. However, together these agents inhibited the release. This suggests that the combination of superoxide and hydrogen peroxide can evoke secretory release. The lytic release of histamine, as monitored by concomitant release of 51Cr from mast cells at higher concentration of xanthine oxidase or longer periods of incubation, seems to be related to hydrogen peroxide production since catalase inhibited the cell lysis. Since it has been reported that exogenously added hydrogen peroxide at concentrations below 10 mM did not induce cell lysis, the lytic release, although hydrogen peroxide dependent, may not be due to its direct effect on the cell surface. The cell lysis observed in the xanthine-xanthine oxidase system seems to be brought about by a complex mechanism involving the interactions of hydrogen peroxide and superoxide with cellular components. These studies indicate that the beneficial effects of superoxide dismutase seen in biological systems may partly be due to inhibition of the secretory processes stimulated by superoxide.
开展本研究以表征由黄嘌呤 - 黄嘌呤氧化酶系统产生的活性氧的性质，该系统通过非细胞毒性和细胞毒性机制参与组胺释放。为了区分分泌性释放和溶解性释放，用51Cr标记肥大细胞，并将51Cr释放到孵育培养基中作为细胞裂解的指标。单独使用超氧化物歧化酶或过氧化氢酶不会抑制组胺的分泌性释放。然而，这两种试剂共同作用时会抑制释放。这表明超氧化物和过氧化氢的组合可引发分泌性释放。在较高浓度的黄嘌呤氧化酶或较长孵育时间下，通过肥大细胞中51Cr的伴随释放监测到的组胺溶解性释放似乎与过氧化氢的产生有关，因为过氧化氢酶可抑制细胞裂解。由于已有报道称，浓度低于10 mM的外源性添加过氧化氢不会诱导细胞裂解，因此尽管溶解性释放依赖于过氧化氢，但可能并非由于其对细胞表面的直接作用。在黄嘌呤 - 黄嘌呤氧化酶系统中观察到的细胞裂解似乎是由一种复杂机制引起的，该机制涉及过氧化氢和超氧化物与细胞成分的相互作用。这些研究表明，在生物系统中观察到的超氧化物歧化酶的有益作用可能部分归因于对由超氧化物刺激的分泌过程的抑制。
