Date on Master's Thesis/Doctoral Dissertation

5-2014

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Committee Chair

Cai, Lu

Subject

Fibroblast growth factors; Testis--Diseases

Abstract

Fibroblast growth factor (FGF)-1 was found to protect the heart from oxidative damage, but clinically its long-term use was restricted for its undesirable proliferating activity on cells. Thus a cluster of amino acids responsible for the proliferation were deleted in the native FGF-1 to create a non-mitogenic FGF-1 (nmFGF-1). To assess whether nmFGF-1 protects male germ cells from diabetes-induced apoptotic death, the study employed a murine model of diabetes using multiple low-doses of streptozotocin, followed by nmFGF-1 treatment for 6 months. Diabetic mice showed a decrease in testicular weight and an increase in apoptotic cell death. Treatment with nmFGF-1 alleviated diabetic effects on testicular weight and apoptotic cell death. Mechanistically, nmFGF-1 alleviated diabetes-induced germ cell death by decreasing the BAX/Bcl-2 ratio, endoplasmic reticulum stress and associated cell death. Our results suggest that nmFGF-1 application prevents apoptotic cell death in testes of diabetic mice from mediation which was associated with Nrf-2 and AKT activation.

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