title: Preventive effect of non-mitogenic acidic fibroblast growth factor on diabetes-induced testicular cell death.
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). Whether the nmFGF-1 protects male germ cells from diabetes-induced apoptotic death was examined in diabetic mice induced with 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 the diabetic effects on testicular weight and apoptotic cell death. Mechanistically, nmFGF-1 may alleviate diabetes-induced germ cell death by decreasing the BAX/Bcl-2 ratio and endoplasmic reticulum stress as well as associated cell death, which is associated with Nrf-2 activation.
authors.affiliation: Department of Pharmacology and Toxicology, The University of Louisville, Louisville 40202, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Skibba
authors.affiliation: The Chinese-American Research Institute for Diabetic Complications, School of Pharmaceutical Sciences & Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China; The Chinese-American Research Institute for Diabetic Complications, the RuiAn Center of Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology of the First Hospital of Jilin University, Changchun 130021, China; KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202, USA; Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Department of Pharmacology and Toxicology, The University of Louisville, Louisville 40202, USA; The Chinese-American Research Institute for Diabetic Complications, School of Pharmaceutical Sciences & Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China; KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202, USA. Electronic address: l0cai001@louisville.edu.
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D013737:Testis / Q000187:drug effects*
chemical_list: D016220:Fibroblast Growth Factor 1
keywords: Diabetic infertility; FGF-1; Germ cell apoptosis; Testicular effect; Type 1 diabetes