title: Protection by sulforaphane from type 1 diabetes-induced testicular apoptosis is associated with the up-regulation of Nrf2 expression and function.
abstract: Diabetes-induced testicular apoptosis is predominantly due to increased oxidative stress. The nuclear factor-erythroid 2-related factor 2 (Nrf2), as a master transcription factor in controlling anti-oxidative systems, is able to be induced by sulforaphane (SFN). To examine whether SFN prevents testicular apoptosis, type 1 diabetic mouse model was induced with multiple low-dose streptozotocin. Diabetic and age-matched control mice were treated with and without SFN at 0.5mg/kg daily in five days of each week for 3months and then kept until 6months. Diabetes significantly increased testicular apoptosis that was associated with endoplasmic reticulum stress and mitochondrial cell death pathways, shown by the increased expression of C/EBP homologous protein (CHOP), cleaved caspase-12, Bax to Bcl2 expression ratio, and cleaved caspase-3. Diabetes also significantly increased testicular oxidative damage, inflammation and fibrosis, and decreased germ cell proliferation. All these diabetic effects were significantly prevented by SFN treatment for the first 3months, and the protective effect could be sustained at 3months after SFN treatment. SFN was able to up-regulate Nrf2 expression and function. The latter was reflected by the increased phosphorylation of Nrf2 at Ser40 and expression of Nrf2 downstream antioxidants at mRNA and protein levels. These results suggest that type 1 diabetes significantly induced testicular apoptosis and damage along with increasing oxidative stress and cell death and suppressing Nrf2 expression and function. SFN is able to prevent testicular oxidative damage and apoptosis in type 1 diabetes mice, which may be associated with the preservation of testicular Nrf2 expression and function under diabetic condition.
authors: The First Hospital of Jilin University, Changchun 130021, China; KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202, USA.
authors: Xin
authors: X
authors: Jiang
authors: The First Hospital of Jilin University, Changchun 130021, China; KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202, USA.
authors: Yang
authors: Y
authors: Bai
authors: The First Hospital of Jilin University, Changchun 130021, China; KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202, USA.
authors: Zhiguo
authors: Z
authors: Zhang
authors: 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. Electronic address: xiny@jlu.edu.cn.
authors: Ying
authors: Y
authors: Xin
authors: The First Hospital of Jilin University, Changchun 130021, China; KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202, USA. Electronic address: l0cai001@louisville.edu.
authors: Lu
authors: L
authors: Cai
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D019610:Cytoprotection; D048909:Diabetes Complications / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013454:Sulfoxides; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D018836:Inflammation Mediators; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D013454:Sulfoxides; C016766:sulforaphane
keywords: Endoplasmic reticulum stress; Nrf2; Oxidative damage; Sulforaphane; Testicular apoptosis; Type 1 diabetes