Pigment epithelium derived factor PEDF exerts antioxidative effects in granulosa cells

Recombinant pigment epithelium–derived factor can protect granulosa cell viability in oxidative stress conditions by increasing SOD-1 and GPX- 2 mRNA levels, decreasing the protein level of BAX, and inducing AKT phosphorylation.

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Authors

Hadas Bar-Joseph, Ph.D., Ido Ben-Ami, M.D., Ph.D., Raphael Ron-El, M.D., Ruth Shalgi, Ph.D., Dana Chuderland, Ph.D.

Volume 102, Issue 3, Pages 891-898

Abstract

Objective:

To determine whether supplementing granulosa cells cultures with pigment epithelium–derived factor (PEDF) can protect them from oxidative stress.

Design:

We used either granulosa cell line or human primary granulosa cell culture from women undergoing in vitro fertilization (IVF) treatments.

Setting:

University research facilities.

Animal(s):

Imprinting control region female mice.

Intervention(s):

Recombinant PEDF (rPEDF) was added to cultures of either primary granulosa cell culture or granulosa cell line in the present or absence of H2O2 triggering.

Main Outcome Measure(s):

We followed cell viability with the use of methylthiazolyl tetrazolium assay and tracked PEDF mechanism of action with the use of Western blot analysis, measuring the level of SOD-1 and GPX-1 mRNA, protein level of BAX, and phosphorylation of AKT.

Result(s):

We found that granulosa cell viability and the level of PEDF mRNA were both significantly reduced, in a dose-dependent manner, after exposure to H2O2. The rate of H2O2-induced apoptosis was significantly attenuated in granulosa cells treated with rPEDF. We showed that granulosa cells, of both humans and rodents, express the PEDF receptor, PNPLA2; once stimulated by rPEDF, the cells exhibited phosphorylation of AKT. Finally, we showed that PEDF exerts its antioxidative activity through the AKT signaling pathway.

Read the full text at: http://www.fertstert.org/article/S0015-0282(14)00545-7/fulltext


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Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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