Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.5 (NADH dehydrogenase)
 2,135 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treating bovine epididymal spermatozoa with rutamycin or rotenone inhibited both respiration and motility supported by endogenous substrates. When oxidative phosphorylation had been blocked with various inhibitors, pyruvate was metabolized to yield ATP and restored motility. Fructose, which is metabolized via glycolysis to yield ATP, was also able to resuscitate the cells. Other substrates tested (lactate, acetate, alpha-ketoglutarate, or glyoxylate) were unable to restore motility in rutamycin-treated cells. In the presence of pyruvate, the phosphorylation uncoupler, carbonylcyanide-p-trifluoromethyoxphenylhydrazone, reduced motility and ATP to common levels in untreated cells or cells treated with rutamycin or rotenone. Pyruvate is thus metabolized to produce ATP by a pathway independent of oxidative phosphorylation associated with the electron transport chain. 5-Methoxyindole-2-carboxylic acid, an inhibitor of lipoyldehydrogenase, prevented the increase of motility and ATP in rutamycin-treated cells, indicating that alpha-keto acid oxidation is involved in the production of ATP from pyruvate when rutamycin is present. With pyruvate present, bongkrekic acid, antimycin A, and anaerobiosis eliminated motility, reduced ATP to low levels, and also significantly reduced the rate of pyruvate metabolism. Acetate was produced from pyruvate only when cellular ATP concentrations were low. Decreases in free carnitine concentrations showed that pyruvate initially used was converted to acetylcarnitine. The results indicate that the intramitochondrial lactate dehydrogenase X, which is unique to spermatozoa, allows the NADH resulting from pyruvate oxidation to reduce other pyruvate molecules to lactate. Pyruvate thus competes with, and can substitute for, the NADH dehydrogenase of the electron transport chain. Pyruvate rapidly repletes the acetylcarnitine pool under a variety of conditions.
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PMID:Pyruvate metabolism in bovine epididymal spermatozoa. 83 18

Inheritance of the mitochondrial genome is known to be exclusively maternal. To determine whether the loss of paternal mitochondria could be due to a deficiency of RNA in the spermatozoal mitochondria, the expression of mitochondrial genes was studied in testicular cells at various stages of spermatogenesis and in epididymal spermatozoa. The presence of mitochondrial transcripts was examined by Northern blot analysis using probes for the following mitochondrially encoded genes: 12 S and 16 S ribosomal RNAs and a group of mRNAs including cytochrome oxidase subunits I and II (COI-COII), cytochrome b (cyt b), adenosine triphosphatase (ATPase) subunits 6 and 8, and subunit 1 of the respiratory chain NADH dehydrogenase (ND1). Comparison of total testicular RNA preparations from prepuberal (6, 8, 12, 16, 18, 20, 22, and 30 days old) and sexually mature (45 days old) mice revealed no major qualitative or quantitative differences in the levels of the mitochondrial transcripts described above. Similar results were observed from enriched preparations of type A and B spermatogonia and interstitial cells obtained from the testes of 8-day-old mice. Transcripts for COI-COII, ATPase 6, or ND1 were reduced in amount in the enriched preparations of pachytene spermatocytes, round spermatids, and residual bodies when compared to the amount in total testis or liver RNA. Transcripts of all the mitochondrial genes analyzed were present in RNA preparations isolated from sperm midpiece tails obtained after sonication of epididymal spermatozoa. These studies demonstrate that (a) during testicular development the levels of mitochondrial RNA in total testicular extracts show no major qualitative and quantitative differences; (b) the mitochondrial transcripts in enriched populations of type A and type B spermatogonia are not different from those obtained from total testes extracts; (c) mitochondrial transcript levels gradually decrease in enriched preparations of pachytene spermatocytes, round spermatids, and residual bodies; and (d) the mitochondrial rRNAs and mRNAs encoded by several mitochondrial genes can be isolated from sperm midpiece tails.
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PMID:Mitochondrial gene expression in male germ cells of the mouse. 277 68

A rapid decrease in male fertility in laboratory animals exposed to 1,2-dibromo-3-chloropropane (DBCP) has been suggested to be due, in part, to a postglycolytic inhibition of sperm carbohydrate metabolism. The present studies were performed to identify the specific site of DBCP-induced inhibition of intermediary metabolism. 14CO2 generation by epididymal sperm, isolated from Fischer 344 rats, was measured using radiolabeled tricarboxylic acid (TCA) cycle intermediates: acetyl CoA, citrate, alpha-ketoglutarate, and succinate. There was 0-28% inhibition of CO2 generation after addition of 0.5 mM DBCP and 81-98% inhibition with 3 mM DBCP, with all four substrates. The activities of alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, malate dehydrogenase, and lactate dehydrogenase were not inhibited by DBCP. Since the DBCP-induced inhibition of metabolism of different substrates to CO2 was similar, and since DBCP did not inhibit enzyme activities of glycolysis or the TCA cycle, a common site of inhibition was suspected. In evaluations of mitochondrial electron transport chain activity, DBCP (3 mM) inhibited oxygen consumption resulting from metabolism of endogenous substrates plus alpha-ketoglutarate or malate by about 80%. When succinate, an FAD-dependent oxidation, was used as a substrate, oxygen consumption was not inhibited by DBCP. It is concluded that DBCP inhibits sperm carbohydrate metabolism at the NADH dehydrogenase step in the mitochondrial electron transport chain.
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PMID:A biochemical basis for 1,2-dibromo-3-chloropropane-induced male infertility: inhibition of sperm mitochondrial electron transport activity. 367 26

The glucose transport mechanism of rat epididymal fat cells was reconstituted into egg lecithin liposomes, and their carrier-mediated transport activity ws estimated from the difference in the rates of uptake of D-[3H]glucose and L-[14C]glucose. Insulin increased the glucose transport activity in the plasma membrane-rich fraction while decreasing the activity in the Golgi-rich fraction in agreement with our previous data (Suzuki, K., and Kono, T. (1980) Proc. Natl. Acad. Sci. U. S. A. 77, 2542-2545). The development of the insulin effects was inhibited when cells were exposed to 2,4-dinitrophenol or KCN before the insulin treatment. In addition, the reversal of the insulin effects was blocked upon exposure of insulin-treated cells to 2,4-dinitrophenol or KCN prior to the elimination of the hormone. In contrast, neither development nor reversal of the insulin effects was affected by cycloheximide or puromycin. The temperature coefficients of the transport activities reconstituted from the basal or insulin-treated forms of the plasma membrane-rich or Golgi-rich fractions were all identical. The recoveries of protein, 5'-nucleotidase, UDP-galactose:N-acetylglucosamine galactosyltransferase, and NADH dehydrogenase into subcellular fractions were determined. However, net effects of insulin on the glucose transport activities have remained unknown for lack of an appropriate marker enzyme of the Golgi-like vesicles associated with the transport activity. It is suggested that the glucose transport mechanism is recycled between the plasma membrane-rich and Golgi-rich fractions by an energy-dependent reaction.
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PMID:Energy-dependent and protein synthesis-independent recycling of the insulin-sensitive glucose transport mechanism in fat cells. 701 68

Vinclozolin, a dicarboximide fungicide, is an endocrine disrupting chemical that competes with an androgenic endocrine disruptor compound. Most research has focused on the epigenetic effect of vinclozolin in humans. In terms of ecotoxicology, understanding the effect of vinclozolin on non-target organisms is important. The expression profile of a comprehensive set of genes in the amphipod Hyalella azteca exposed to vinclozolin was examined. The expressed sequence tags in low-dose vinclozolin-treated and -untreated amphipods were isolated and identified by suppression subtractive hybridization. DNA dot blotting was used to confirm the results and establish a subtracted cDNA library for comparing all differentially expressed sequences with and without vinclozolin treatment. In total, 494 differentially expressed genes, including hemocyanin, heatshock protein, cytochrome, cytochrome oxidase and NADH dehydrogenase were detected. Hemocyanin was the most abundant gene. DNA dot blotting revealed 55 genes with significant differential expression. These genes included larval serum protein 1 alpha, E3 ubiquitin-protein ligase, mitochondrial cytochrome c oxidase, mitochondrial protein, proteasome inhibitor, hemocyanin, zinc-finger-containing protein, mitochondrial NADH-ubiquinone oxidoreductase and epididymal sperm-binding protein. Vinclozolin appears to upregulate stress-related genes and hemocyanin, related to immunity. Moreover, vinclozolin downregulated NADH dehydrogenase, related to respiration. Thus, even a non-lethal concentration of vinclozolin still has an effect at the genetic level in H. azteca and presents a potential risk, especially as it would affect non-target organism hormone metabolism.
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PMID:Screening differentially expressed genes in an amphipod (Hyalella azteca) exposed to fungicide vinclozolin by suppression subtractive hybridization. 2519 May 60

Although cryopreservation has been developed and optimized over the past decades, it causes various stresses, including cold shock, osmotic stress, and ice crystal formation, thereby reducing fertility. During cryopreservation, addition of cryoprotective agent (CPA) is crucial for protecting spermatozoa from freezing damage. However, the intrinsic toxicity and osmotic stress induced by CPA cause damage to spermatozoa. To identify the effects of CPA addition during cryopreservation, we assessed the motility (%), motion kinematics, capacitation status, and viability of epididymal spermatozoa using computer-assisted sperm analysis and Hoechst 33258/chlortetracycline fluorescence staining. Moreover, the effects of CPA addition were also demonstrated at the proteome level using two-dimensional electrophoresis. Our results demonstrated that CPA addition significantly reduced sperm motility (%), curvilinear velocity, viability (%), and non-capacitated spermatozoa, whereas straightness and acrosome-reacted spermatozoa increased significantly (p < 0.05). Ten proteins were differentially expressed (two decreased and eight increased) (>3 fold, p < 0.05) after CPA, whereas NADH dehydrogenase flavoprotein 2, f-actin-capping protein subunit beta, superoxide dismutase 2, and outer dense fiber protein 2 were associated with several important signaling pathways (p < 0.05). The present study provides a mechanistic basis for specific cryostresses and potential markers of CPA-induced stress. Therefore, these might provide information about the development of safe biomaterials for cryopreservation and basic ground for sperm cryopreservation.
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PMID:Addition of Cryoprotectant Significantly Alters the Epididymal Sperm Proteome. 2703 3