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1.
Cloning of rat brain succinyl-CoA:3-oxoacid CoA-transferase cDNA. Regulation of the mRNA in different rat tissues and during brain development. 总被引:1,自引:0,他引:1 下载免费PDF全文
M K Ganapathi M Kwon P M Haney C McTiernan A A Javed R A Pepin D Samols M S Patel 《The Biochemical journal》1987,248(3):853-857
3-Oxoacid CoA-transferase, which catalyses the first committed step in the oxidation of ketone bodies, is uniquely regulated in developing rat brain. Changes in 3-oxoacid CoA-transferase activity in rat brain during the postnatal period are due to changes in the relative rate of synthesis of the enzyme. To study the regulation of this enzyme, we identified, with a specific polyclonal rabbit anti-(rat 3-oxoacid CoA-transferase), two positive cDNA clones (approx. 800 bp) in a lambda gtll expression library, constructed from poly(A)+ RNA from brains of 12-day-old rats. One of these clones (lambda CoA3) was subcloned into M13mp18 and subjected to further characterization. Labelled single-stranded probes prepared by primer extension of the M13mp18 recombinant hybridized to a 3.6 kb mRNA. Rat brain mRNA enriched by polysome immunoadsorption for a single protein of size 60 kDa which corresponds to the precursor form of 3-oxoacid CoA-transferase was also found to be similarly enriched for the hybridizable 3.6 kb mRNA complementary to lambda CoA3. Affinity-selected antibody to the lambda CoA3 fusion protein inhibited 3-oxoacid CoA-transferase activity present in rat brain mitochondrial extracts. The 3.6 kb mRNA for 3-oxoacid CoA-transferase was present in relative abundance in rat kidney and heart, to a lesser extent in suckling brain and mammary gland and negligible in the liver. The specific mRNA was also found to be 3-fold more abundant in the brain from 12-day-old rats as compared with 18-day-old foetuses and adult rats, corresponding to the enzyme activity and relative rate of synthesis profile during development. These data suggest that 3-oxoacid CoA-transferase enzyme activity is regulated at a pretranslational level. 相似文献
2.
Hardies SC; Martin SL; Voliva CF; Hutchison CA d; Edgell MH 《Molecular biology and evolution》1986,3(2):109-125
3.
Chathurika Henpita Rajesh Vyas Chastity L. Healy Tra L. Kieu Aditi U. Gurkar Matthew J. Yousefzadeh Yuxiang Cui Aiping Lu Luise A. Angelini Ryan D. O'Kelly Sara J. McGowan Sanjay Chandrasekhar Rebecca R. Vanderpool Danielle Hennessy-Wack Mark A. Ross Timothy N. Bachman Charles McTiernan Smitha P. S. Pillai Warren Ladiges Mitra Lavasani Johnny Huard Donna Beer-Stolz Claudette M. St. Croix Simon C. Watkins Paul D. Robbins Ana L. Mora Eric E. Kelley Yinsheng Wang Timothy D. O'Connell Laura J. Niedernhofer 《Aging cell》2023,22(4):e13782
Cardiomyopathy is a progressive disease of the myocardium leading to impaired contractility. Genotoxic cancer therapies are known to be potent drivers of cardiomyopathy, whereas causes of spontaneous disease remain unclear. To test the hypothesis that endogenous genotoxic stress contributes to cardiomyopathy, we deleted the DNA repair gene Ercc1 specifically in striated muscle using a floxed allele of Ercc1 and mice expressing Cre under control of the muscle-specific creatinine kinase (Ckmm) promoter or depleted systemically (Ercc1−/D mice). Ckmm-Cre+/−;Ercc1−/fl mice expired suddenly of heart disease by 7 months of age. As young adults, the hearts of Ckmm-Cre+/−;Ercc1−/fl mice were structurally and functionally normal, but by 6-months-of-age, there was significant ventricular dilation, wall thinning, interstitial fibrosis, and systolic dysfunction indicative of dilated cardiomyopathy. Cardiac tissue from the tissue-specific or systemic model showed increased apoptosis and cardiac myocytes from Ckmm-Cre+/-;Ercc1−/fl mice were hypersensitive to genotoxins, resulting in apoptosis. p53 levels and target gene expression, including several antioxidants, were increased in cardiac tissue from Ckmm-Cre+/−;Ercc1−/fl and Ercc1−/D mice. Despite this, cardiac tissue from older mutant mice showed evidence of increased oxidative stress. Genetic or pharmacologic inhibition of p53 attenuated apoptosis and improved disease markers. Similarly, overexpression of mitochondrial-targeted catalase improved disease markers. Together, these data support the conclusion that DNA damage produced endogenously can drive cardiac disease and does so mechanistically via chronic activation of p53 and increased oxidative stress, driving cardiac myocyte apoptosis, dilated cardiomyopathy, and sudden death. 相似文献
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5.
Furha Iram Cossor Lucile L. Adams-Campbell Rowan T. Chlebowski Marc J. Gunter Karen Johnson Robert E. Martell Anne McTiernan Michael S. Simon Thomas Rohan Robert B. Wallace Jessica K. Paulus 《Cancer epidemiology》2013,37(5):742-749
Background: Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin's influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women's Health Initiative (WHI) clinical trials and observational study. Methods: 2066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n = 84); women with diabetes with no metformin use (n = 128); and women without diabetes (n = 1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results: After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40–1.38, p = 0.67) and to women without diabetes (HR 1.00; 95% CI 0.61–1.66, p = 0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38–1.55, p = 0.47) and for overall survival was 0.86 (95% CI 0.49–1.52; p = 0.60). Conclusions: In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted. 相似文献
6.
McTiernan A Sorensen B Irwin ML Morgan A Yasui Y Rudolph RE Surawicz C Lampe JW Lampe PD Ayub K Potter JD 《Obesity (Silver Spring, Md.)》2007,15(6):1496-1512
Objectives: The effect of national exercise recommendations on adiposity is unknown and may differ by sex. We examined long‐term effects of aerobic exercise on adiposity in women and men. Research Methods and Procedures: This was a 12‐month randomized, controlled clinical trial testing exercise effect on weight and body composition in men (N = 102) and women (N = 100). Sedentary/unfit persons, 40 to 75 years old, were recruited through physician practices and media. The intervention was facility‐ and home‐based moderate‐to‐vigorous intensity aerobic activity, 60 min/d, 6 days/wk vs. controls (no intervention). Results: Exercisers exercised a mean 370 min/wk (men) and 295 min/wk (women), and seven dropped the intervention. Exercisers lost weight (women, ?1.4 vs. +0.7 kg in controls, p = 0.008; men, ?1.8 vs. ?0.1 kg in controls, p = 0.03), BMI (women, ?0.6 vs. +0.3 kg/m2 in controls, p = 0.006; men, ?0.5 kg/m2 vs. no change in controls, p = 0.03), waist circumference (women, ?1.4 vs. +2.2 cm in controls, p < 0.001; men, ?3.3 vs. ?0.4 cm in controls, p = 0.003), and total fat mass (women, ?1.9 vs. +0.2 kg in controls, p = 0.001; men, ?3.0 vs. +0.2 kg in controls, p < 0.001). Exercisers with greater increases in pedometer‐measured steps per day had greater decreases in weight, BMI, body fat, and intra‐abdominal fat (all p trend < 0.05 in both men and women). Similar trends were observed for increased minutes per day of exercise and for increases in maximal oxygen consumption. Discussion: These data support the U.S. Department of Agriculture and Institute of Medicine guidelines of 60 min/d of moderate‐to‐vigorous physical activity. 相似文献
7.
Roberto?H?Higa Roberto?C?Togawa Arnaldo?J?Montagner Juliana?CF?Palandrani Igor?KS?Okimoto Paula?R?Kuser Michel?EB?Yamagishi Adauto?L?Mancini Goran?NeshichEmail author 《BMC bioinformatics》2004,5(1):107
Background
The integration of many aspects of protein/DNA structure analysis is an important requirement for software products in general area of structural bioinformatics. In fact, there are too few software packages on the internet which can be described as successful in this respect. We might say that what is still missing is publicly available, web based software for interactive analysis of the sequence/structure/function of proteins and their complexes with DNA and ligands. Some of existing software packages do have certain level of integration and do offer analysis of several structure related parameters, however not to the extent generally demanded by a user. 相似文献8.
Kadokami T McTiernan CF Kubota T Frye CS Bounoutas GS Robbins PD Watkins SC Feldman AM 《American journal of physiology. Heart and circulatory physiology》2001,280(5):H2281-H2291
Tumor necrosis factor (TNF)-alpha plays a key role in the pathogenesis of septic shock syndrome, and myocardial TNF-alpha expression may contribute to this pathophysiology. We examined the myocardial expression of TNF-alpha-related cytokines and chemokines in mice exposed to lipopolysaccharide (LPS) and tested the effects of anti-TNF therapy on myocardial cytokine expression. Cytokine mRNA levels were measured by RNase protection assay, and protein levels in the plasma and myocardium were assessed by enzyme-linked immunosorbent assays. LPS (4 microg/g body wt ip) induced marked cytokine expression, including TNF-alpha, interleukin (IL)-1beta, IL-6, and monocyte chemotactic protein (MCP)-1, in both the plasma and myocardium. Pretreatment with adenovirus-mediated TNF receptor fusion protein (AdTNFR1; 10(9) plaque-forming units iv) decreased plasma cytokine levels. In contrast, whereas myocardial IL-1beta expression was also suppressed, expression of IL-6 and MCP-1 was not inhibited by AdTNFR1. In summary, anti-TNF treatment differentially altered the cytokine expression in the plasma and myocardium during endotoxemia. Inability to block myocardial expression of IL-6 and MCP-1 suggests a possible mechanism for the failure of anti-TNF therapies in the treatment of endotoxin shock. 相似文献
9.
Interest in the use of low-copy nuclear genes for phylogenetic analyses of
plants has grown rapidly, because highly repetitive genes such as those
commonly used are limited in number. Furthermore, because low- copy genes
are subject to different evolutionary processes than are plastid genes or
highly repetitive nuclear markers, they provide a valuable source of
independent phylogenetic evidence. The gene for granule-bound starch
synthase (GBSSI or waxy) exists in a single copy in nearly all plants
examined so far. Our study of GBSSI had three parts: (1) Amino acid
sequences were compared across a broad taxonomic range, including grasses,
four dicotyledons, and the microbial homologs of GBSSI. Inferred structural
information was used to aid in the alignment of these very divergent
sequences. The informed alignments highlight amino acids that are conserved
across all sequences, and demonstrate that structural motifs can be highly
conserved in spite of marked divergence in amino acid sequence. (2)
Maximum-likelihood (ML) analyses were used to examine exon sequence
evolution throughout grasses. Differences in probabilities among
substitution types and marked among-site rate variation contributed to the
observed pattern of variation. Of the parameters examined in our set of
likelihood models, the inclusion of among-site rate variation following a
gamma distribution caused the greatest improvement in likelihood score. (3)
We performed cladistic parsimony analyses of GBSSI sequences throughout
grasses, within tribes, and within genera to examine the phylogenetic
utility of the gene. Introns provide useful information among very closely
related species, but quickly become difficult to align among more divergent
taxa. Exons are variable enough to provide extensive resolution within the
family, but with low bootstrap support. The combined results of amino acid
sequence comparisons, maximum-likelihood analyses, and phylogenetic studies
underscore factors that might affect phylogenetic reconstruction. In this
case, accommodation of the variable rate of evolution among sites might be
the first step in maximizing the phylogenetic utility of GBSSI.
相似文献
10.