生殖医学と活性酸素 : 消去系
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概要
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Reactive oxygen species such as superoxide anion (O_2^^-), hydrogen peroxide (H_2O_2) and hydroxy radical (OH) posses potent oxygen toxicity to cells. Superoxide dismutases (SODs) are metalloenzymes that are essential for dismutation of O_2^^- to H_2O_2 and O_2. SODs are important initial components in the cellular defense against oxygen toxicity since O_2^^- can react with H_2O_2 to generate single oxygen and hydroxy radicals, which are even more reactive and cytotoxic than O_2^^- or H_2O_2. In mammalian tissues three superoxide dismutases (SODs) designated Cu, Zn-SOD, Mn-SOD and extracellular SOD exist. These enzymes play an important role in the antioxidant defense system against superoxide anion (O_2^^-) generated in vivo and may be involved in various pathophysiological processes including inflammation, cancer diabetes, aging and ischemia. (1)The role of superoxide anion in ovulation and luteal function was investigated the localization of Cu, Zn-SOD and Mn-SOD in rat and human ovary by immunohistochemical methods. Cu, Zn-SOD was present in granulosa cells of mature Graafian follicles and growing follicles and Mn-SOD was present in luteal cells of the corpus luteum in rat. (2)To investigate the relationship between active oxygen radical-scavenge system and ovulatory mechanism in human. Mn-SOD was found in granulosa cells and theca cells of mature follicles, luteal cells of corpus luteum and epithelial cells of fallopian tubes. Cu, Zn-SOD was localized in theca cells of mature follicles, margin of corpus luteum and epithelial cells of tubal isthmus. Mn-SOD and Cu, Zn-SOD have a different localization and action in the human ovary and fallopian tube, and oxygen radicals-SOD system may play an important role in ovulation and luteal function in human ovary. (3)The concentration of Mn-SOD in maternal blood decreased as gestation progress. Northern blot analysis of Mn-SOD mRNA for trophoblast during pregnancy indicated that trophoblast of midpregnancy contained elevated levels of message of Mn-SOD. (4)An enzyme-linked immunosorbent assay has been developed to detect serum Mn-SOD. With this assay, only 0.9% of the 207 healthy females tested had more than 120 ng per milliliter of serum Mn-SOD. In contrast, 69 of 106 patients (65%) with epithelial ovarian carcinomas showed high levels of Mn-SOD. The serum Mn-SOD increased according to the clinical stage and declined to reflect the effects of therapy. Compared with CA 125, Mn-SOD showed a less frequent false positive rate (10%) in benign gynecological diseases. The determination of Mn-SOD levels proved to be a clinically useful marker for monitoring the response to treatment and to early detection of the recurrence of epithelial ovarian carcinomas. (5)Marked increase in protein levels of Mn-SOD was found in TNF-resistant cell lines after treatment with tumor necrosis factor (TNF). Mn-SOD was responsive to TNF stimulation in KURAMOCHI, a human ovarian adenocarcinoma TNF-resistant cell line. This may explain above mentioned result that Mn-SOD protein is highly expressed in epithelial ovarian cancer.
- 1993-08-01
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