Dihydrolipoamide dehydrogenase and cAMP are associated with cadmium-mediated Leydig cell damage

Cytotoxic mechanism related to dihydrolipoamide dehydrogenase in Leydig cells exposed to heavy metals

“…Gunnarsson et al (2003), reported that acute subcutaneous injection of Cd (10 mg/kg) reduced testicular cAMP concentrations after 48 and 144 h. In the review of (Thevenod (2009), Cd and cAMP signaling was discussed: variable effects on cAMP levels depending on the cell type investigated and the dose or concentration of Cd used in the experiments; the knowledge of a differential regulation of the various adenylate cyclase (AC) and cAMP phosphodiesterase (PDE) isoforms as well as their differential expression in various tissues needs to be considered in future studies to unravel the apparent disparity of effects of acute or chronic Cd exposure in different organs and cells. Our results suggested that DLD may be one of the initial steps in the steroidogenic signaling pathway and be involved in the regulation of cAMP levels in Leydig cells exposed to heavy metals (Zhang et al, 2011). DLD is the third component of pyruvate dehydrogenase complex, a-ketoglutarate dehydrogenase complex, and branched chain keto acid dehydrogenase complex (Patel and Roche, 1990).…”

“…The molecular mechanism related to mitochondria in Leydig cell exposed to heavy metals is still unclear. Our earlier studies demonstrated that there were 34 protein spots with altered expression identified by 2DE-based proteomics technology in Leydig cells R2C exposed to Cd, and dihydrolipoamide dehydrogenase (DLD) was hubs in the network of those proteins with a most significant decreased expression; meanwhile, intracellular levels of cyclic AMP (cAMP) also decreased in a dose dependent manner in Leydig cells with exposure of Cd (Zhang et al, 2011). Gunnarsson et al (2003), reported that acute subcutaneous injection of Cd (10 mg/kg) reduced testicular cAMP concentrations after 48 and 144 h. In the review of (Thevenod (2009), Cd and cAMP signaling was discussed: variable effects on cAMP levels depending on the cell type investigated and the dose or concentration of Cd used in the experiments; the knowledge of a differential regulation of the various adenylate cyclase (AC) and cAMP phosphodiesterase (PDE) isoforms as well as their differential expression in various tissues needs to be considered in future studies to unravel the apparent disparity of effects of acute or chronic Cd exposure in different organs and cells.…”

Oxidative Stress and Antioxidants in Disease and Cancer: A Review

“…Besides mitochondria, many enzymes are also capable of producing ROS. These include, but not limited to, NADPH oxidase (Bylund et al, 2010), xanthine oxidase (Agarwal et al, 2011), α-ketoglutarate dehydrogenase complex (Ambrus et al, 2011), d-amino acid oxidases (Fang et al, 2012), and dihydrolipoamide dehydrogenase (Zhang et al, 2011;Kareyeva et al, 2012).…”

Ameliorative potentials of a combination of fenugreek and alpha-tocopherol on cadmium induced testicular toxicity: an ultrastructural study

“…It is noted that fenugreek consumption restored serum testosterone level and testicular weight [45]. The fenugreek being an antioxidant, it performs a crucial role in restoring testosterone level by eliminating ROS which is known to stop steroidogenesis [45,60].…”