Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009443 (cold)
 92,137 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemia-reperfusion injury, a major cause of organ metabolic alterations and consequent dysfunction in liver transplantation, could be overcome by optimizing organ preservation procedures. The potential of autofluorescence analysis was investigated with the aim to define parameters suitable for in vivo monitoring tissue functionality. Spectrofluorometric analysis was performed on explanted rat livers during cold storage, under standard (4 degrees C University of Wisconsin medium for 20 h) and purposely damaging (4 degrees C Eurocollins medium for 20, 43 and 72 h) preservation conditions, and reperfusion (rewarming-reoxygenation). For both preservation conditions, cold hypoxia caused a signal amplitude increase, mainly attributable to NAD(P)H, and a spectral shape modification, ascribable to changes in the relative contributions of NAD(P)H and flavins, as a result of the tissue reduced state enhancement. Upon rewarming-reoxygenation the autofluorescence signal decreased with a rate depending on the preservation conditions. The time constant changed according to the extent of the liver functionality impairment, as assessed by conventional biochemical and histochemical analyses, thus providing a parameter exploitable for an in situ, real time monitoring of the efficacy of experimental preservation procedures.
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PMID:Autofluorescence spectroscopy of rat liver during experimental transplantation procedure. An approach for hepatic metabolism assessment. 1605 63

Chilling injury is sustained by dry pollen of Typha latifolia L. upon hydration in germination medium at 0 degrees C. This injury is evidenced as poor germination, low vigor, and depressed respiration. Isolated mitochondria showed multiple sites of impaired electron transport. Besides losses of cytochrome (Cyt) c and NAD(+), the activities of membrane-bound enzyme complexes such as Cyt oxidase, NADH-duroquinone oxidoreductase, succinate-duroquinone oxidoreductase, and malate-duroquinone oxidoreductase were severely affected.Similarly, as in isolated mitochondria, in situ tests of mitochondrial activity showed that Cyt c was partially lost from its site of action. Re-addition of the lost Cyt c to the grains restored the N,N,N',N'-tetramethyl p-phenylenediamine dihydrochloride plus ascorbate-mediated electron transport from Cyt c to O(2), but did not significantly accelerate the overall O(2) uptake. Electron flow to duroquinone in the injured grains was low, indicating that lesions at the substrate side of ubiquinone determine the rate of O(2) consumption. Leakage of NAD(+), and also of adenylate phosphates and Krebs cycle substrates out of the injured grains, was considerable.Increasing the initial moisture content of the grains strongly enhanced their resistance to cold hydration. Below 17% moisture content (fresh weight basis), the decrease in vigor closely matched the loss of NAD(+) and adenosine phosphates. Vitality was irreversibly lost by cold hydration below 10 to 12% initial moisture content.Injury to dry pollen was prevented by imbibition at 27 degrees C. Decrease of vigor and increased leakage, however, started below 20 degrees C, and complete loss of vitality occurred below 10 degrees C.These results are interpreted as evidence that loss of membrane integrity is the primary cause of imbibitional chilling injury.
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PMID:Imbibitional chilling injury in pollen: involvement of the respiratory chain. 1666 16

An NAD(+)-dependent alcohol dehydrogenase of a psychrotorelant from Antarctic seawater, Flavobacterium frigidimaris KUC-1 was purified to homogeneity with an overall yield of about 20% and characterized enzymologically. The enzyme has an apparent molecular weight of 160k and consists of four identical subunits with a molecular weight of 40k. The pI value of the enzyme and its optimum pH for the oxidation reaction were determined to be 6.7 and 7.0, respectively. The enzyme contains 2 gram-atoms Zn per subunit. The enzyme exclusively requires NAD(+) as a coenzyme and shows the pro-R stereospecificity for hydrogen transfer at the C4 position of the nicotinamide moiety of NAD(+). F. frigidimaris KUC-1 alcohol dehydrogenase shows as high thermal stability as the enzymes from thermophilic microorganisms. The enzyme is active at 0 to over 85 degrees C and the most active at 70 degrees C. The half-life time and k (cat) value at 60 degrees C were calculated to be 50 min and 27,400 min(-1), respectively. The enzyme also shows high catalytic efficiency at low temperatures (0-20 degrees C) (k(cat)/K(m) at 10 degrees C; 12,600 mM(-1)min(-1)) similar to other cold-active enzymes from psychrophiles. The alcohol dehydrogenase gene is composed of 1,035 bp and codes 344 amino acid residues with an estimated molecular weight of 36,823. The sequence identities were found with the amino acid sequences of alcohol dehydrogenases from Moraxella sp. TAE123 (67%), Pseudomonas aeruginosa (65%) and Geobacillus stearothermophilus LLD-R (56%). This is the first example of a cold-active and thermostable alcohol dehydrogenase.
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PMID:A cold-active and thermostable alcohol dehydrogenase of a psychrotorelant from Antarctic seawater, Flavobacterium frigidimaris KUC-1. 1707 83

NAD-dependent l-glutamate dehydrogenase (NAD-GDH) activity was detected in cell extract from the psychrophile Janthinobacterium lividum UTB1302, which was isolated from cold soil and purified to homogeneity. The native enzyme (1,065 kDa, determined by gel filtration) is a homohexamer composed of 170-kDa subunits (determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis). Consistent with these findings, gene cloning and sequencing enabled deduction of the amino acid sequence of the subunit, which proved to be comprised of 1,575 amino acids with a combined molecular mass of 169,360 Da. The enzyme from this psychrophile thus appears to belong to the GDH family characterized by very large subunits, like those expressed by Streptomyces clavuligerus and Pseudomonas aeruginosa (about 180 kDa). The entire amino acid sequence of the J. lividum enzyme showed about 40% identity with the sequences from S. clavuligerus and P. aeruginosa enzymes, but the central domains showed higher homology (about 65%). Within the central domain, the residues related to substrate and NAD binding were highly conserved, suggesting that this is the enzyme's catalytic domain. In the presence of NAD, but not in the presence of NADP, this GDH exclusively catalyzed the oxidative deamination of l-glutamate. The stereospecificity of the hydride transfer to NAD was pro-S, which is the same as that of the other known GDHs. Surprisingly, NAD-GDH activity was markedly enhanced by the addition of various amino acids, such as l-aspartate (1,735%) and l-arginine (936%), which strongly suggests that the N- and/or C-terminal domains play regulatory roles and are involved in the activation of the enzyme by these amino acids.
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PMID:Gene cloning and characterization of the very large NAD-dependent l-glutamate dehydrogenase from the psychrophile Janthinobacterium lividum, isolated from cold soil. 1752 98

Sirtuin genes function as anti-aging genes in yeast, Caenorhabditis elegans, and Drosophila. The NAD requirement for sirtuin function indicates a link between aging and metabolism, and a boost in sirtuin activity may in part explain how calorie restriction extends life span. In mammals, one of the substrates of the SIR2 ortholog, SIRT1, is a regulator of mitochondrial biogenesis, PGC-1alpha. Indeed, the putative SIRT1 activator resveratrol has been shown to stimulate mitochondrial biogenesis and deliver health benefits in treated mice. I explore here how mitochondrial biogenesis may have beneficial effects on aging and, perhaps, diseases of aging. In particular, I speculate that SIRT1-mediated mitochondrial biogenesis may reduce the production of reactive oxygen species, a possible cause of aging, and offer two possible mechanisms for this effect. An understanding of how calorie restriction works may lead to novel drugs to combat diseases of aging.
Cold Spring Harb Symp Quant Biol 2007
PMID:Sirtuins in aging and disease. 1841 8

We studied changes induced by cold on electron transfer pathways (linked to NADH or NADPH oxidation) in endoplasmic reticulum of rapeseed hypocotyls (Brassica napus L.) from a freezing-sensitive variety (ISL) and freezing-tolerant variety (Tradition). Plantlets were grown at 22 degrees C then submitted to a cold shock of 13 or 35 days at 4 degrees C. We measured the content in NADH, NADPH, NAD and NADP of the hypocotyls and the redox power was estimated by the reduced versus oxidized nucleotide ratio. The contents in cytochromes b (5) and P-450, electron acceptors of NADH and NADPH respectively, were determined by differential spectrophotometry. Finally, activity of both NADH-cytochrome b (5) reductase (E.C.1.6.2.2) and NADPH cytochrome P-450 reductase (E.C.1.6.2.4) was determined by reduction of exogenous cytochrome c. Results show that during cold shock, along with an increase of linolenic acid content, there was a general activation of the NADPH pathway which was observed more quickly in Tradition plantlets than in ISL ones. Due to transfer of electrons that can occur between NADPH reductase and cytochrome b (5), this could favor fatty acid desaturation in Tradition, explaining why linolenic acid accumulation was more pronounced in this variety. Besides, more cytochrome P-450 accumulated in ISL that could compete for electrons needed by the FAD3 desaturase, resulting in a relative slower enrichment in 18:3 fatty acid in these plantlets.
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PMID:Changes in electron transport pathways in endoplasmic reticulum of rapeseed in response to cold. 1866 70

Polyhydroxyalkanoates (PHAs) are highly reduced bacterial storage compounds that increase fitness in changing environments. We have previously shown that phaRBAC genes from the Antarctic bacterium Pseudomonas sp. 14-3 are located in a genomic island containing other genes probably related with its adaptability to cold environments. In this paper, Pseudomonas sp. 14-3 and its PHA synthase-minus mutant (phaC) were used to asses the effect of PHA accumulation on the adaptability to cold conditions. The phaC mutant was unable to grow at 10 degrees C and was more susceptible to freezing than its parent strain. PHA was necessary for the development of the oxidative stress response induced by cold treatment. Addition of reduced compounds cystine and gluthathione suppressed the cold sensitive phenotype of the phaC mutant. Cold shock produced very rapid degradation of PHA in the wild type strain. The NADH/NAD ratio and NADPH content, estimated by diamide sensitivity, decreased strongly in the mutant after cold shock while only minor changes were observed in the wild type. Accordingly, the level of lipid peroxidation in the mutant strain was 25-fold higher after temperature downshift. We propose that PHA metabolism modulates the availability of reducing equivalents, contributing to alleviate the oxidative stress produced by low temperature.
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PMID:Polyhydroxyalkanoates are essential for maintenance of redox state in the Antarctic bacterium Pseudomonas sp. 14-3 during low temperature adaptation. 1893 22

Sirtuin family of proteins possesses NAD-dependent deacetylase and ADP ribosyltransferase activities. They are found to respond to nutrient deprivation and profoundly regulate metabolic functions. We have previously reported that caloric restriction increases the expression of one of the seven mammalian sirtuins, SIRT2, in tissues such as white adipose tissue. Because adipose tissue is a key metabolic organ playing a critical role in whole body energy homeostasis, we went on to explore the function of SIRT2 in adipose tissue. We found short-term food deprivation for 24 h, already induces SIRT2 expression in white and brown adipose tissues. Additionally, cold exposure elevates SIRT2 expression in brown adipose tissue but not in white adipose tissue. Intraperitoneal injection of a beta-adrenergic agonist (isoproterenol) enhances SIRT2 expression in white adipose tissue. Retroviral expression of SIRT2 in 3T3-L1 adipocytes promotes lipolysis. SIRT2 inhibits 3T3-L1 adipocyte differentiation in low-glucose (1 g/l) or low-insulin (100 nM) condition. Mechanistically, SIRT2 suppresses adipogenesis by deacetylating FOXO1 to promote FOXO1's binding to PPARgamma and subsequent repression on PPARgamma transcriptional activity. Overall, our results indicate that SIRT2 responds to nutrient deprivation and energy expenditure to maintain energy homeostasis by promoting lipolysis and inhibiting adipocyte differentiation.
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PMID:SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma. 1903 6

Sirtuins are NAD(+)-dependent protein deacetylases. They mediate adaptive responses to a variety of stresses, including calorie restriction and metabolic stress. Sirtuin 3 (SIRT3) is localized in the mitochondrial matrix, where it regulates the acetylation levels of metabolic enzymes, including acetyl coenzyme A synthetase 2 (refs 1, 2). Mice lacking both Sirt3 alleles appear phenotypically normal under basal conditions, but show marked hyperacetylation of several mitochondrial proteins. Here we report that SIRT3 expression is upregulated during fasting in liver and brown adipose tissues. During fasting, livers from mice lacking SIRT3 had higher levels of fatty-acid oxidation intermediate products and triglycerides, associated with decreased levels of fatty-acid oxidation, compared to livers from wild-type mice. Mass spectrometry of mitochondrial proteins shows that long-chain acyl coenzyme A dehydrogenase (LCAD) is hyperacetylated at lysine 42 in the absence of SIRT3. LCAD is deacetylated in wild-type mice under fasted conditions and by SIRT3 in vitro and in vivo; and hyperacetylation of LCAD reduces its enzymatic activity. Mice lacking SIRT3 exhibit hallmarks of fatty-acid oxidation disorders during fasting, including reduced ATP levels and intolerance to cold exposure. These findings identify acetylation as a novel regulatory mechanism for mitochondrial fatty-acid oxidation and demonstrate that SIRT3 modulates mitochondrial intermediary metabolism and fatty-acid use during fasting.
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PMID:SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. 2020 11

All bacteria share a set of evolutionarily conserved essential genes that encode products that are required for viability. The great diversity of environments that bacteria inhabit, including environments at extreme temperatures, place adaptive pressure on essential genes. We sought to use this evolutionary diversity of essential genes to engineer bacterial pathogens to be stably temperature-sensitive, and thus useful as live vaccines. We isolated essential genes from bacteria found in the Arctic and substituted them for their counterparts into pathogens of mammals. We found that substitution of nine different essential genes from psychrophilic (cold-loving) bacteria into mammalian pathogenic bacteria resulted in strains that died below their normal-temperature growth limits. Substitution of three different psychrophilic gene orthologs of ligA, which encode NAD-dependent DNA ligase, resulted in bacterial strains that died at 33, 35, and 37 degrees C. One ligA gene was shown to render Francisella tularensis, Salmonella enterica, and Mycobacterium smegmatis temperature-sensitive, demonstrating that this gene functions in both Gram-negative and Gram-positive lineage bacteria. Three temperature-sensitive F. tularensis strains were shown to induce protective immunity after vaccination at a cool body site. About half of the genes that could be tested were unable to mutate to temperature-resistant forms at detectable levels. These results show that psychrophilic essential genes can be used to create a unique class of bacterial temperature-sensitive vaccines for important human pathogens, such as S. enterica and Mycobacterium tuberculosis.
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PMID:Essential genes from Arctic bacteria used to construct stable, temperature-sensitive bacterial vaccines. 2062 65


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