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Am J Physiol Endocrinol Metab. 2014 Jul 1;307(1):E14-23. doi: 10.1152/ajpendo.00702.2013. Epub 2014 May 6.

Sulforaphane reduction of testicular apoptotic cell death in diabetic mice is associated with the upregulation of Nrf2 expression and function.

Author information

1
China-Japan Union Hospital of Jilin University, Changchun, China; Kosair Children's Hospital Research Institute, the Department of Pediatrics of the University of Louisville, Louisville, Kentucky;
2
Kosair Children's Hospital Research Institute, the Department of Pediatrics of the University of Louisville, Louisville, Kentucky; The First Hospital of Jilin University, Changchun, China;
3
Kosair Children's Hospital Research Institute, the Department of Pediatrics of the University of Louisville, Louisville, Kentucky; The Second Hospital of Jilin University, Changchun, China;
4
China-Japan Union Hospital of Jilin University, Changchun, China;
5
Department of Pediatrics, Division of Endocrinology, University of Louisville, Wendy L. Novak Diabetes Care Center, Kosair Children's Hospital, Louisville, Kentucky; and.
6
China-Japan Union Hospital of Jilin University, Changchun, China; haibian76@163.com.
7
Kosair Children's Hospital Research Institute, the Department of Pediatrics of the University of Louisville, Louisville, Kentucky; Departments of Radiation Oncology, Pharmacology, and Toxicology, University of Louisville, Louisville, Kentucky.

Abstract

Diabetes-induced testicular cell death is due predominantly to oxidative stress. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is an important transcription factor in controlling the antioxidative system and is inducible by sulforaphane (SFN). To test whether SFN prevents diabetes-induced testicular cell death, an insulin-defective stage of type 2 diabetes (IDS-T2DM) was induced in mice. This was accomplished by feeding them a high-fat diet (HFD) for 3 mo to induce insulin resistance and then giving one intraperitoneal injection of streptozotocin to induce hyperglycemia while age-matched control mice were fed a normal diet (ND). IDS-T2DM and ND-fed control mice were then further subdivided into those with or without 4-mo SFN treatment. IDS-T2DM induced significant increases in testicular cell death presumably through receptor and mitochondrial pathways, shown by increased ratio of Bax/Bcl2 expression and cleavage of caspase-3 and caspase-8 without significant change of endoplasmic reticulum stress. Diabetes also significantly increased testicular oxidative damage and inflammation. All of these diabetic effects were significantly prevented by SFN treatment with upregulated Nrf2 expression. These results suggest that IDS-T2DM induces testicular cell death presumably through caspase-8 activation and mitochondria-mediated cell death pathways and also by significantly downregulating testicular Nrf2 expression and function. SFN upregulates testicular Nrf2 expression and its target antioxidant expression, which was associated with significant protection of the testis from IDS-T2DM-induced germ cell death.

KEYWORDS:

high-fat diet; male germ cell death; nuclear factor (erythroid-derived 2)-like 2; sulforaphane; type 2 diabetes

PMID:
24801392
DOI:
10.1152/ajpendo.00702.2013
[Indexed for MEDLINE]
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