Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A full-length cDNA encoding the sperm-specific enzyme lactate dehydrogenase-C4 was isolated from a fox testis cDNA expression library and sequenced. The deduced translated protein sequence was shown to be 86% identical to that of human LDH-C4. In the fox testis, mRNA encoding LDH-C4 was first detected in pachytene spermatocytes. The LDH-C4 protein monomer was identified in Western blots of sperm membrane extracts as having a molecular weight of approximately 35,000, consistent with the monomeric size of this subunit previously identified in sperm from other species. The LDH-C4 protein is localized on the sperm plasma membrane overlying the principal piece of the tail. Based on the available sequence data, we were able to identify an epitope within the N-terminal region of the LDH-C4 amino-acid sequence which when administered to female foxes is antigenic and produces antibodies capable of recognizing the native protein.
Mol Reprod Dev 1996 Aug
PMID:Cloning, sequencing, and characterization of LDH-C4 from a fox testis cDNA library. 884 87

The LDH release pattern from cardiomyocytes under 'ischemia-like' conditions shows two phases. In the initial slow phase, reoxygenation immediately stops further enzyme release. Accelerated LDH release, which occurs concomitantly with Iysosomal enzyme release, characterizes the second phase of 'ischemia.' Reoxygenation at this stage does not put a stop to further enzyme release. Reoxygenation during the first phase of 'ischemia' rapidly restored ATP level, while in the second phase, ATP levels remained low even after 6 h of reoxygenation. This study as well as previous data seem to suggest that irreversible cellular damage leading to cell death, occurs by synergistic action of many effectors, each of which does not necessarily cause irreversible damage.
Mol Cell Biochem
PMID:Reversible and irreversible damage in reoxygenated 'ischemic' ventricular myocytes in culture. 890 67

Primary cultures enriched in neurons dissociated from embryonic rat cerebral cortex, cerebellum, or hippocampus were treated in a chemically defined serum-free media with either vehicle, dodecylglycerol (DDG, 3 microM), or glutamate (75 microM), or preincubated with DDG for 4 or 24 h, and further incubated with glutamate. Their morphological and biochemical assessments (lactate dehydrogenase [LDH] release in the culture media, neuronal viability and intracellular Ca2+ mobilization) were made. Neurotoxic effects of glutamate and glutamate-mediated increases in intracellular Ca2+ were maximal in neurons from cerebellum and minimal in neurons from cortex. Cotreatment of cells with DDG and glutamate failed to provide significant neuronal protection against glutamate in the three brain regions. Pretreatment of cells with DDG for 4 or 24 h prior to glutamate treatment provided significant neuroprotection as judged by morphological changes and a decrease in LDH activity. Neuroprotection of approximately 15-35% was observed following 4 h of DDG pretreatment, increasing to 60-85% protection after 24 h of DDG pretreatment. Although the mechanism of DDG's neuroprotective action remains to be elucidated, these results demonstrate that both glutamate and DDG have differential specificity for anatomical regions of the brain.
Mol Chem Neuropathol
PMID:Dodecylglycerol provides partial protection against glutamate toxicity in neuronal cultures derived from different regions of embryonic rat brain. 913 22

We assessed the role of .NO in recombinant adenovirus-mediated gene transfer both in vitro and in vivo. NIH3T3 fibroblasts, stably transfected with the human inducible nitric oxide synthase, but lacking tetrahydrobiopterin (NIH3T3/iNOS [inducibile nitric oxide synthase]), were infected with replication-deficient adenovirus (E1-deleted), containing either the luciferase or the Lac Z reporter genes (AdCMV-Luc and AdCMV-Lac Z; 1-10 plaque forming units [pfu]/cell). Incubation of infected cells with sepiapterin (50 microM), a precursor of tetrahydrobiopterin, progressively increased nitrate/nitrite levels in the medium and decreased both luciferase and beta-galactosidase protein expression to approximately 60% of their corresponding control values, 24 h later. NIH3T3/iNOS cells had normal ATP (adenosine 5'-triphosphate) levels and did not release LDH(lactic dehydrogenase) into the medium. Pretreatment of these cells with N(G)-monomethyl-L-arginine (L-NMMA; 1 mM), an inhibitor of iNOS, prevented the sepiapterin-mediated induction of .NO and restored gene transfer to baseline values. Incubation of NIH3T3/iNOS with 8-bromo-cGMP (400 microM) in the absence of sepiapterin, or exposure of AdCMV-Luc to large concentrations of .NO, did not alter the efficacy of gene transfer. .NO produced by NIH3T3/iNOS cells also suppressed beta-galactosidase expression in NIH3T3 cocultured cells stably transfected with beta-galactosidase gene, suggesting .NO inhibited gene expression at either the transriptional or posttranscriptional levels. To investigate the effects of inhaled .NO on gene transfer in vivo, CD1 mice received an intratracheal instillation of AdCMV-Luc (4 x 10(9) pfu in 80 microl of saline) and exposed to .NO (25 ppm in room air) for 72 h. At that time, no significant degree of lung inflammation was detected by histological examination. However, lung luciferase activity decreased by 53% as compared with air breathing controls (P < 0.05; n > or = 8). We concluded that overproduction of .NO decreases the efficiency of adenovirus-mediated gene transfer in lung cells in the absence of cytotoxicity or inflammation.
Am J Respir Cell Mol Biol 1997 May
PMID:Modulation of adenovirus-mediated gene transfer by nitric oxide. 916 Aug 30

We measured the effect of urea on M4-lactate dehydrogenase (M4-LDH) from elasmobranchs and Australian desert frogs (urea accumulators) and from two animals that do not accumulate urea, the axolotl and the rabbit. An analysis of the effect of urea on the Kd(NADH), V, V/K(m(prr)) and V/K(m(NADH)) shows that in all cases the major effect of urea was on the binding of pyruvate, which fits with data in the literature that show that urea acts as a competitive inhibitor of LDH. The characteristics of the elasmobranch enzymes are consistent with a proposed adaptation model, but the situation for the enzymes from the aestivating frogs is equivocal. Urea (400 mM) had less effect on the K(m(prr)) of M4-LDH from the urea accumulators than it did on the non-accumulators, suggesting a general adaptation and that the enzyme produced by the aestivating frogs (urea accumulators) is kinetically different from that of non-aestivating frogs (non-accumulators). A new approach is used to characterize the overall pattern of adaptation to urea. The pattern is similar in an enzyme from an elasmobranch and an aestivating frog despite the temporary presence of urea in the latter and the phylogenetic difference between these animals.
Comp Biochem Physiol B Biochem Mol Biol 1997 May
PMID:Effects of urea on M4-lactate dehydrogenase from elasmobranchs and urea-accumulating Australian desert frogs. 918 22

Spontaneously immortalized fibroblast cell lines derived from embryonic tissues of C3D2F1, mice were analyzed for loss of heterozygosity (LOH) at multiple chromosomal loci to identify candidate suppressor loci for immortalization. Among 47 simple sequence repeat (SSR) loci selected for screening, those on chromosome 4 exhibited an exceptionally high LDH incidence of up to 89%. Only four other chromosomes (8, 11, 12, and 18) showed LOH, with the highest incidence being 33%. To further localize candidate suppressor genes on mouse chromosome 4, detailed deletion mapping was performed with 18 cell lines and 14 SSR markers. The greatest LOH incidence (94%) was observed at the D4Mit14 locus located on distal chromosome 4, indicating that a major suppressor gene resides in this region. On the other hand, at the D4Mit77 locus, 30 cM proximal to the D4Mit14 locus, we found the SSR to be homozygously lost in 39% of the cell lines. Because the D4Mit77 is tightly linked to the tumor suppressor gene p16, for which homozygous deletion has been reported in various human tumor cell lines, we also examined our fibroblast cell lines for gross aberrations of the p16 gene by using the Southern blot method. The p16 gene was found to be homozygously deleted in 56% of the cell lines. Although this result implies that the p16 gene plays a role as a suppressor gene for immortalization, the combined incidence of LOH and homozygous deletion at the D4Mit77 locus was 72%, which is significantly lower than the observed incidence at the D4Mit14 locus. Consequently, we concluded that immortalization of mouse embryonic fibroblasts may involve more than one suppressor gene on chromosome 4.
Mol Carcinog 1997 May
PMID:Loss of heterozygosity at loci on chromosome 4, a common genetic event during the spontaneous immortalization of mouse embryonic fibroblasts. 918 Sep 24

In vivo administration of either 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or methamphetamine (MA) produces damage to the dopaminergic nervous system which may be due in part to the generation of reactive oxygen species (ROS). The resistance of superoxide dismutase (SOD) over-expressing transgenic mice to the effects of both MPTP and MA suggests the involvement of superoxide in the resulting neurotoxicity of both compounds. Superoxide can be converted by SOD to hydrogen peroxide, which itself can cause cellular degeneration by reacting with free iron to produce highly reactive hydroxyl radicals resulting in damage to proteins, nucleic acids and membrane phospholipids. Hydrogen peroxide has also been reported to be produced via inhibition of NADH dehydrogenase by MPP + formed during oxidation of MPTP by MAO-B and by dopamine auto-oxidation following MA-induced dopamine release from synaptic vesicles within nerve terminals. To test whether hydrogen peroxide is an important factor in the toxicity of either of these two neurotoxins, we created clonal PC12 lines expressing elevated levels of the hydrogen peroxide-reducing enzyme glutathione peroxidase (GSHPx). Elevation of GSHPx levels in PC12 was found to diminish the rise in ROS levels and lipid peroxidation resulting from MA but not MPTP treatment. Elevated levels of GSHPx also appeared to prevent decreases in transport-mediated dopamine uptake produced via MA administration as well as to attenuate toxin-induced cell loss as measured by either MTT reduction or LDH release. Our data, therefore, suggest that hydrogen peroxide production likely contributes to MA toxicity in dopaminergic neurons.
Brain Res Mol Brain Res 1997 Jun
PMID:Elevated expression of glutathione peroxidase in PC12 cells results in protection against methamphetamine but not MPTP toxicity. 919 Oct 89

Using an isolated ferret heart preparation (Langendorff perfusion, perfusion pressure 90 mmHg), energy metabolism has been characterized in right and left ventricles from control and hypertrophied hearts. Hypertrophy was induced by pulmonary artery clipping for 30-45 days (right ventricle wall weight/body weight ratio increased by 70%). Myocardial contents of high energy phosphate compounds, glycogen and lactate, and the activities of some enzymes were biochemically measured in perfused hearts and also after ischemic arrest (30 min global ischemia). In hypertrophied right ventricles, PCr (-46%), Cr (-34%) levels, creatine kinase activity (-18%) were significantly decreased compared with control. ATP and Pi levels were not affected by hypertrophy. The adenylate energy charges were similar (0.85-0.86) in both types of heart. The activities of hexokinase (+26%), aldolase (+212%), pyruvate kinase (+14%) and glucose 6-phosphate dehydrogenase (+107%) were increased by hypertrophy. The LDH isozyme pattern was significantly changed such that LDH3 was decreased by 11%, and LDH4 and LDH5 were increased by a factor 1.4 and 2.9 respectively in hypertrophy. After 30 min of global ischemia, PCr level was decreased by 89 and 79% in control and hypertrophied ventricles respectively. ATP level was depressed by 41 in control and only by 21% in hypertrophied muscles. Altogether, the present data suggested that, in the adult ferret heart, the capacity for the ATP synthesis could be maintained during hypertrophy by the enhancement of the glycolytic pathway. The smaller decline of ATP after ischemia in hypertrophied tissue could be explained by a lower consumption of ATP in the hypertrophied compared to the control heart during the earliest period of ischemia.
J Mol Cell Cardiol 1997 Jul
PMID:Energy metabolism in normal and hypertrophied right ventricle of the ferret heart. 923 44

We examined the in vitro preconditioning effect of non-toxic derivative of endotoxin, monophosphoryl lipid A (MLA) in adult rat cardiac myocytes. Cultured 5-7-day-old myocytes were preconditioned for 4 h by treatment with 200 ng/ml MLA. Twenty h later, cells were subjected to simulated ischemia by incubation in 0.75 mm sodium hydrosulfite, 12 mM KCl, 20 mM dl-lactic acid and 10 mM 2-deoxy-D-glucose (pH 6.5) for 2 h. MLA caused a significant reduction in the levels of LDH from 286+/-8 units/l in controls to 165+/-5 units/l (mean+/-s.e.m.; P<0.0001). Similarly, CK significantly decreased from 104+/-3.1 in controls to 85+/-1.4 U/l (P<0.001). Western blot analysis indicated a significant accumulation of 72 kD heat shock protein in MLA treated as compared to control cells. No changes in 27, 32, and 90 kD heat shock proteins were discernible in the MLA treated group. These data suggest a significant "anti-ischemic" effect of MLA in myocytes that is accompanied by induction of 72 kD heat shock protein.
J Mol Cell Cardiol 1997 Aug
PMID:Monophosphoryl lipid A protects adult rat cardiac myocytes with induction of the 72-kD heat shock protein: a cellular model of pharmacologic preconditioning. 928 61

The effect of several antioxidants and cysteine-elevating precursor drugs (prodrugs) was tested on lens damage occurring after in vitro exposure to low levels of 60Co-gamma-irradiation, to simulate in vitro the exposure to radiation in vivo of (1) astronauts (2) jet crews (3) military radiation accident personnel. Tocopherol (100 microM), ascorbic acid (1 mM), R-alpha-lipoic acid (1 mM), and taurine (0.5 mM) protected against radiation-associated protein leakage. MTCA and ribocysteine protected lenses against opacification, LDH and protein leakage, indicating that antioxidants and prodrugs of cysteine appear to offer protection against lens damage caused by low level radiation.
Biochem Mol Biol Int 1997 Sep
PMID:Antioxidants and cataract: (cataract induction in space environment and application to terrestrial aging cataract). 930 37


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