Changes in activities of superoxide dismutase and lipid peroxide in corpus luteum during pregnancy in rats

Sugino, Norihiro; Nakamura, Yasuhiko; Takeda, Orie; Ishimatsu, Masaru; Katô, Hiroshi

doi:10.1530/jrf.0.0970347

Cited by 68 publications

(51 citation statements)

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“…The enzyme encoded by this gene is expressed in the rat corpus luteum of pregnancy and protects the gland against toxic oxygen radicals by scavenging superoxide radicals (Sugino et al 1993). We have previously shown that LPS stimulated Mn-SOD expression in pregnant rat corpora lutea within 2 h of treatment (Sugino et al 1998b), which coincides with the induction of NF B/DNA binding induced by the endotoxin in our present study.…”

Section: Discussionsupporting

confidence: 81%

Involvement of nuclear factor kappa B in the regulation of rat luteal function: potential roles as survival factor and inhibitor of 20alpha-hydroxysteroid dehydrogenase

Telleria

Goyeneche

Stocco³

et al. 2004

Journal of Molecular Endocrinology

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Nuclear factor kappa B (NF B) is an important intracellular conveyor of extracellular signals and modulates a number of gene responses. Due to the potential significance of NF B in regulating ovarian gene expression, we examined in the rat: (i) whether NF B is activated and developmentally regulated in the corpus luteum (CL) throughout pregnancy; (ii) the proteins forming the NF B complex in luteal cells; and (iii) the role of this transcription factor in luteal function. Western analysis and immunohistochemistry revealed that p65 and p50 were highly expressed throughout pregnancy and were located in both the nucleus and cytoplasm of luteal cells. In addition, because NF B is maintained in the cytoplasm bound to I B, whose phosphorylation allows NF B translocation to the nucleus, we studied the developmental expression of phosphorylated and nonphosphorylated forms of I B . Western analysis revealed that I B was present and phosphorylated throughout pregnancy in the CL whereas by protein/DNA array and electromobility shift assays we found that luteal nuclear extracts bind to an NF B consensus sequence, and that the binding activity decreased along pregnancy. The specific binding was supershifted only by an anti-p65 antibody and not by antibodies against p50, p52, cRel, or RelB. Using day 4 postpartum ovaries, we found higher NF B binding activity in the newly formed CL than in old CL of pregnancy. Furthermore, NF B DNA binding activity was enhanced by prolactin in luteinized granulosa cells. In our first functional study, blockade of NF B/p65 binding to DNA with the sesquiterpene lactone helenalin in luteinized granulosa cells correlated with induction of cell death in a dose-dependent manner. In a second functional study, overexpression of NF B/p65 in luteal cells resulted in inhibition of 20 -hydroxysteroid dehydrogenase (20 HSD) promoter activity as well as endogenous 20 HSD mRNA expression. In summary, we have shown that: (i) NF B is expressed within the CL, primary luteinized granulosa cells, and a rat luteal cell line; (ii) NF B activation within the CL is developmentally regulated in pregnancy, depends on the age of the gland, and can be upregulated by prolactin; (iii) inhibition of NF B/p65 binding to an NF B DNA consensus sequence correlates with induction of cell death in ovarian luteinized granulosa cells; and (iv) overexpression of NF B in luteal cells inhibits 20 HSD gene expression. The results further support a role for NF B as a survival factor in the CL.

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Section: Discussionsupporting

confidence: 81%

Involvement of nuclear factor kappa B in the regulation of rat luteal function: potential roles as survival factor and inhibitor of 20alpha-hydroxysteroid dehydrogenase

Telleria

Goyeneche

Stocco³

et al. 2004

Journal of Molecular Endocrinology

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“…Evidence has also accumulated to suggest that locally produced antioxidant enzymes within the CL are directly involved in the maintenance of luteal steroidogenic activity and possibly in the rescue of CL from luteolysis when pregnancy occurs in various mammalian species. This includes (1) the changes in SOD1 and manganese SOD2 activities in the rat CL in a manner similar to the change in serum progesterone concentrations throughout pregnancy (Sugino et al 1993a) and pseudopregnancy (Shimamura et al 1995), (2) the high level of expression of the extracellular SOD (EC-SOD or SOD3), SOD2 and catalase in the bovine CL during early pregnancy (Rueda et al 1995), (3) the high expression and activity of SOD1 in human CL during early pregnancy (Sugino et al 2000), (4) the ability of SOD1 and catalase to stimulate the secretion of progesterone in vivo by rat CL of late pregnancy (Sugino et al 1993b) and (5) the isolation and identification of sheep SOD1 from the CL of pregnancy (Al-Gubory et al 2003). The inhibition of nuclear DNA cleavage, characteristic of physiological cell death (apoptosis), in cultured isolated rabbit CL with SOD, catalase or a putative stimulator of endogenous GPX (Dharmarajan et al 1999), the induction of apoptotic DNA fragmentation in bovine luteal cells by down-regulation of GPX ) and the induction of apoptosis in cultured bovine luteal cells by simultaneous treatment with H 2 O 2 and with a specific inhibitor of GPX ) suggest a role for ROS in luteal cell apoptosis.…”

mentioning

confidence: 99%

Antioxidant enzymatic defence systems in sheep corpus luteum throughout pregnancy

Al-Gubory¹,

Bolifraud²,

Germain³

et al. 2004

Reproduction

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The activities of copper, zinc-superoxide dismutase (SOD1), manganese SOD (SOD2), glutathione peroxidase (GPX), glutathione reductase (GSSG-R) and glutathione S-transferase (GST) were studied in sheep corpora lutea (CL) obtained on days 15, 40, 60, 80 and 128 of pregnancy. Maintained enzymatic activity of SOD1, SOD2, GPX, GSSG-R and GST were found in the sheep CL throughout pregnancy. Enzymatic activity of SOD1, GPX and GST increased significantly from day 15 to day 40 of pregnancy, and thereafter remained constant until day 128. SOD2 and GSSG-R activities were not different between any days of pregnancy examined. Apoptotic luteal cells identified by the terminal deoxynucleotidyl transferase-mediated fluoresceindUTP nick-end labelling were very rarely observed, and their incidence (less than 0.5%) was not different between days of pregnancy. These results showed that the activities of antioxidant enzymes in the sheep CL are subject to major changes during early pregnancy, suggesting that the CL of early pregnancy may be rescued from luteolysis through increasing activities of key antioxidant enzymes and inhibition of apoptosis. Maintained levels of antioxidant enzymes in the CL throughout pregnancy may be linked to reactive oxygen species continuously generated in the steroidogenically active luteal cells, and may be involved in the maintenance of luteal steroidogenic activity and cellular integrity.

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“…C u , Z n -S O D a c t i v i t y w a s determined as reported previously [41]. The amount of protein required for 50% inhibition in the absorbance at 550 nm was defined as one unit (nitrite unit=NU) of SOD activity.…”

Section: Sod Assaymentioning

confidence: 99%

Withdrawal of Ovarian Steroids Stimulates Prostaglandin F2.ALPHA. Production Through Nuclear Factor-.KAPPA.B Activation via Oxygen Radicals in Human Endometrial Stromal Cells: Potential Relevance to Menstruation

et al. 2004

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Abstract. The present study was undertaken to investigate whether withdrawal of estrogen and progesterone (EP-withdrawal) stimulates prostaglandin F2α (PGF2α) production through oxygen radical (ROS)-induced NF-κB activation in human endometrial stromal cells (ESC). To study the EPwithdrawal, ESC that had been treated with estradiol (E, 10 -8 M) and medroxyprogesterone acetate (MPA, 10 -6 M) for 12 days were then incubated with or without E+MPA for a further 11 days. PGF2α concentrations in the medium and cyclooxygenase-2 (COX-2) mRNA levels were significantly increased after EP-withdrawal, while they were unchanged by the continuous treatment with E+MPA. When ESC were incubated with N-acetyl-L-cysteine (Nac, 50 mM), an antioxidant, during EP-withdrawal, Nac blocked the increases in PGF2α production and COX-2 mRNA expression caused by EPwithdrawal. Next, we examined whether ROS generated in response to EP-withdrawal acted through NF-κB activation. Electrophoretic mobility shift assay revealed that EP-withdrawal caused marked increases in NF-κB DNA binding activity, which was completely suppressed by Nac. Furthermore, when ESC were incubated with MG132 (3 µM), which inhibits NF-κB activation, during EPwithdrawal, MG132 blocked the increases in PGF2α production and COX-2 mRNA expression caused by EP-withdrawal. In conclusion, EP-withdrawal stimulates COX-2 expression and PGF2α production through ROS-induced NF-κB activation, suggesting a possible mechanism for menstruation. Key words: Endometrial stromal cell, Prostaglandin F2α, NF-κB, Superoxide dismutase, Superoxide radical (J. Reprod. Dev. 50: [215][216][217][218][219][220][221][222][223][224][225] 2004) eactive oxygen species (ROS), including superoxide radicals, cause cell damage, whereas superoxide dismutase (SOD) is an enzyme specific to scavenging superoxide radicals and protects cells from oxygen radical cytotoxicity. Oxidative stress and its defense system have been reported to play important roles in the regulation of reproductive function [1][2][3][4][5][6][7]. In the human endometrium, SOD activities decrease and ROS levels increase in the late secretory phase, just before menstruation, suggesting that these changes in SOD and ROS may be involved in endometrial breakdown [8]. Recently, much attention has been focused on the reports that ROS act as second messengers in the regulation of cellular function [9-

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Changes in activities of superoxide dismutase and lipid peroxide in corpus luteum during pregnancy in rats

Cited by 68 publications

References 0 publications

Involvement of nuclear factor kappa B in the regulation of rat luteal function: potential roles as survival factor and inhibitor of 20alpha-hydroxysteroid dehydrogenase

Involvement of nuclear factor kappa B in the regulation of rat luteal function: potential roles as survival factor and inhibitor of 20alpha-hydroxysteroid dehydrogenase

Antioxidant enzymatic defence systems in sheep corpus luteum throughout pregnancy

Withdrawal of Ovarian Steroids Stimulates Prostaglandin F2.ALPHA. Production Through Nuclear Factor-.KAPPA.B Activation via Oxygen Radicals in Human Endometrial Stromal Cells: Potential Relevance to Menstruation

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