• PMID: 27289041
• Gene Name: DLD
• Condition: Regulates sperm motility, Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Regulates sperm motility, Male infertility

Tyrosine phosphorylation of dihydrolipoamide dehydrogenase as a potential cadmium target and its inhibitory role in regulating mouse sperm motility

Li X, Wang L, Li Y, Fu J, Zhen L, Yang Q, Li S, Zhang Y.

Cadmium (Cd) is reported to reduce sperm motility and functions. However, the molecular mechanisms of Cd-induced toxicity remain largely unknown, presenting a major knowledge gap in research on reproductive toxicology. In the present study, we identified a candidate protein, dihydrolipoamide dehydrogenase (DLD), which is a post-pyruvate metabolic enzyme, exhibiting tyrosine phosphorylation in mouse sperm exposed to Cd both in vivo and in vitro. Immunoprecipitation assay demonstrated DLD was phosphorylated in tyrosine residues without altered expression after Cd treatment, which further confirmed our identified result. However, the tyrosine phosphorylation of DLD did not participate in mouse sperm capacitation and Bovine Serum Albumin (BSA) effectively prevented the tyrosine phosphorylation of DLD. Moreover, Cd-induced tyrosine phosphorylation of DLD lowered its dehydrogenase activity and meanwhile, Nicotinamide Adenine Dinucleotide Hydrogen (NADH) content, Adenosine Triphosphate (ATP) production and sperm motility were all inhibited by Cd. Interestingly, when the tyrosine phosphorylation of DLD was blocked by BSA, the decrease of DLD activity, NADH and ATP content as well as sperm motility was also suppressed simultaneously. These results suggested that Cd-induced tyrosine phosphorylation of DLD inhibited its activity and thus suppressed the tricarboxylic acid (TCA) cycle, which resulted in the reduction of NADH and hence the ATP production generated through oxidative phosphorylation (OPHOXS). Taken together, our results revealed that Cd induced DLD tyrosine phosphorylation, in response to regulate TCA metabolic pathway, which reduced ATP levels and these negative effects led to decreased sperm motility. This study provided new understanding of the mechanisms contributing to the harmful effects of Cd on the motility and function of spermatozoa. CI - Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. FAU - Li, Xinhong AU - Li X AD - Shanghai Key Lab of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiaotong University, Shanghai 200240, China. Electronic address: lixinhong7172@sjtu.edu.cn. FAU - Wang, Lirui AU - Wang L AD - Shanghai Key Lab of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiaotong University, Shanghai 200240, China. FAU - Li, Yuhua AU - Li Y AD - Shanghai Key Lab of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiaotong University, Shanghai 200240, China. FAU - Fu, Jieli AU - Fu J AD - Shanghai Key Lab of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiaotong University, Shanghai 200240, China. FAU - Zhen, Linqing AU - Zhen L AD - Shanghai Key Lab of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiaotong University, Shanghai 200240, China. FAU - Yang, Qiangzhen AU - Yang Q AD - Shanghai Key Lab of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiaotong University, Shanghai 200240, China. FAU - Li, Sisi AU - Li S AD - Shanghai Key Lab of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiaotong University, Shanghai 200240, China.