A novel functional role of nickel in sperm motility and eukaryotic cell growth.

BACKGROUND: Metal ions are essential for numerous life processes. This study aims to investigate the relationship between seminal quality and ion levels in seminal plasma. BASIC PROCEDURES: A total of 205 semen samples were collected and seminal plasma ion levels were examined with inductively-coupled plasma-mass spectrometry. The nickel function was demonstrated by in vitro assay and cell growth. MAIN FINDINGS: The low sperm motility group showed distinctively reduced nickel concentration in seminal plasma compared with the normal sperm motility group. However, arsenic, sulfur, selenium, magnesium and zinc were negatively associated with sperm quality. No significant relationship between other examined cations and semen quality was observed. In vitro assay suggested low concentration of nickel significantly increased sperm total motility and progressive motility. Cell growth assay further confirmed nickel promoted eukaryotic yeast cell growth. Nickel level in seminal plasma may play important functions to determine sperm quality. PRINCIPAL CONCLUSIONS: Our study reveals a strong correlation between S, Mg, Se, Zn, As, Ni and seminal quality as well as discovers a novel functional role of nickel in sperm motility and eukaryotic cell growth. These findings may provide a potential avenue for assessment of sperm quality and treatment of reproduction disorders.

Activation of hepatic CREBH and Insig signaling in the anti-hypertriglyceridemic mechanism of R-α-lipoic acid.

The activation of sterol regulatory element binding proteins (SREBPs) is regulated by insulin-induced genes 1 and 2 (Insig-1 and Insig-2) and SCAP. We previously reported that feeding R-α-lipoic acid (LA) to Zucker diabetic fatty (ZDF) rats improves severe hypertriglyceridemia. In this study, we investigated the role of cyclic AMP-responsive element binding protein H (CREBH) in the lipid-lowering mechanism of LA and its involvement in the SREBP-1c and Insig pathway. Incubation of McA cells with LA (0.2 mM) or glucose (6 mM) stimulated activation of CREBH. LA treatment further induced mRNA expression of Insig-1 and Insig-2a, but not Insig-2b, in glucose-treated cells. In vivo, feeding LA to obesity-induced hyperlipidemic ZDF rats activated hepatic CREBH and stimulated transcription and translation of Insig-1 and Insig-2a. Activation of CREBH and Insigs induced by LA suppressed processing of SREBP-1c precursor into nuclear SREBP-1c, which subsequently inhibited expression of genes involved in fatty acid synthesis, including FASN, ACC and SCD-1, and reduced triglyceride (TG) contents in both glucose-treated cells and ZDF rat livers. Additionally, LA treatment also decreased abundances of very low density lipoprotein (VLDL)-associated apolipoproteins, apoB100 and apoE, in glucose-treated cells and livers of ZDF rats, leading to decreased secretion of VLDL and improvement of hypertriglyceridemia. This study unveils a novel molecular mechanism whereby LA lowers TG via activation of hepatic CREBH and increased expression of Insig-1 and Insig-2a to inhibit de novo lipogenesis and VLDL secretion. These findings provide novel insight into the therapeutic potential of LA as an anti-hypertriglyceridemia dietary molecule.