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Emilie Martinez Nicolas Gérard Maira M. Garcia Andrzej Mazur Rosa-Maria Guéant-Rodriguez Blandine Comte Jean-Louis Guéant Patrick Brachet 《The Journal of nutritional biochemistry》2013,24(7):1241-1250
Methyl donor (MD: folate, vitamin B12 and choline) deficiency causes hyperhomocysteinemia, a risk factor for cardiovascular diseases. However, the mechanisms of the association between MD deficiency, hyperhomocysteinemia, and cardiomyopathy remain unclear. Therefore, we performed a proteomic analysis of myocardium of pups from rat dams fed a MD-depleted diet to understand the impact of MD deficiency on heart at the protein level. Two-dimension gel electrophoresis and mass spectrometry-based analyses allowed us to identify 39 proteins with significantly altered abundance in MD-deficient myocardium. Ingenuity Pathway Analysis showed that 87% of them fitted to a single protein network associated with developmental disorder, cellular compromise and lipid metabolism. Concurrently increased protein carbonylation, the major oxidative post-translational protein modification, could contribute to the decreased abundance of many myocardial proteins after MD deficiency. To decipher the effect of MD deficiency on the abundance of specific proteins identified in vivo, we developed an in vitro model using the cardiomyoblast cell line H9c2. After a 4-day exposure to a MD-deprived (vs. complete) medium, cells were deficient of folate and vitamin B12, and released abnormal amounts of homocysteine. Western blot analyses of pup myocardium and H9c2 cells yielded similar findings for several proteins. Of specific interest is the result showing increased and decreased abundances of prohibitin and α-crystallin B, respectively, which underlines mitochondrial injury and endoplasmic reticulum stress within MD deficiency. The in vitro findings validate the MD-deficient H9c2 cells as a relevant model for studying mechanisms of the early metabolic changes occurring in cardiac cells after MD deprivation. 相似文献
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Jill A. Jablonowski Kiev S. Ly Michael Bogenstaetter Curt A. Dvorak Jamin D. Boggs Lisa K. Dvorak Brian Lord Kirsten L. Miller Curt Mazur Sandy J. Wilson Timothy W. Lovenberg Nicholas I. Carruthers 《Bioorganic & medicinal chemistry letters》2009,19(3):903-907
A novel series of imidazole containing histamine H3 receptor ligands were investigated and found to be potent functional antagonists. After improving the stability of these molecules towards liver microsomes, these compounds were found to have no appreciable affinity for CYP P450s. Subsequent in vivo experiments showed significant brain uptake of (4-chloro-phenyl)-[2-(1-isopropyl-piperidin-4-ylmethoxy)-3-methyl-3H-imidazol-4-yl]-methanone 22. 相似文献
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Aleksandra Pawlak Witold Gładkowski Justyna Kutkowska Marcelina Mazur Bożena Obmińska-Mrukowicz Andrzej Rapak 《Bioorganic & medicinal chemistry letters》2018,28(7):1171-1177
For many years, studies focused on developing new natural or synthetic compounds with antineoplastic activity have attracted the attention of researchers. An interesting group of such compounds seem to be those with both lactone moiety and an aromatic ring which, in addition to antimicrobial or antiviral activity, also exhibit antitumor properties. The study shows antitumor activity of two enantiomeric trans isomers of 5-(1-iodoethyl)-4-(2′,5′-dimethylphenyl)dihydrofuran-2-one. Our aim was to determine their antitumor activity manifested as an ability to induce apoptosis in selected canine cancer cell lines as well as to evaluate differences in their strength depending on the configuration of their stereogenic centers. The enantiomers (+)-(4R,5S,6R)-1 and (?)-(4S,5R,6S)-2 were found to induce classical caspase-dependent apoptosis through downregulation of the expression of anti-apoptotic proteins Bcl-xL and Bcl-2. Although the mechanism of apoptosis induction was the same for both enantiomers, they differed in their strength, as stronger antineoplastic activity in vitro was exhibited by isomer (+)-(4R,5S,6R)-1. 相似文献
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M. M. Mazur †‡ M. T. Wilson † A. B. Dougherty † A. Buchheister † D. A. Beauchamp § 《Journal of fish biology》2007,70(3):816-836
A bioenergetics model for juvenile age‐0 year walleye pollock Theragra chalcogramma was applied to a spatially distinct grid of samples in the western Gulf of Alaska to investigate the influence of temperature and prey quality on size‐specific growth. Daily growth estimates for 50, 70 and 90 mm standard length (LS) walleye pollock during September 2000 were generated using the bioenergetics model with a fixed ration size. Similarities in independent estimates of prey consumption generated from the bioenergetics model and a gastric evacuation model corroborated the performance of the bioenergetics model, concordance correlation (rc) = 0·945, lower 95% CL (transformed) (L1) = 0·834, upper 95% CL (transformed) (L2) = 0·982, P < 0·001. A mean squared error analysis (MSE) was also used to partition the sources of error between both model estimates of consumption into a mean component (MC), slope component (SC), and random component (RC). Differences between estimates of daily consumption were largely due to differences in the means of estimates (MC= 0·45) and random sources (RC= 0·49) of error, and not differences in slopes (SC= 0·06). Similarly, daily growth estimates of 0·031–0·167 g day?1 generated from the bioenergetics model was within the range of growth estimates of 0·026–0·190 g day?1 obtained from otolith analysis of juvenile walleye pollock. Temperature and prey quality alone accounted for 66% of the observed variation between bioenergetics and otolith growth estimates across all sizes of juvenile walleye pollock. These results suggest that the bioenergetics model for juvenile walleye pollock is a useful tool for evaluating the influence of spatially variable habitat conditions on the growth potential of juvenile walleye pollock. 相似文献
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Freeze-cleaving can be used as a direct probe to examine the ultrastructural alterations of biological material due to freezing. We examined the thesis that at least two factors, which are oppositely dependent upon cooling velocity, determine the survival of cells subjected to freezing. According to this thesis, when cells are cooled at rates exceeding a critical velocity, a decrease in viability is caused by the presence of intracellular ice; but cells cooled at rates less than this critical velocity do not contain appreciable amounts of intracellular ice and are killed by prolonged exposure to a solution that is altered by the presence of ice. As a test of this hypothesis, we examined freeze-fractured replicas of the yeast Saccharomyces cerevisiae after suspensions had been cooled at rates ranging from 1.8 to 75,000°C/min. Some of the frozen samples were cleaved and replicated immediately in order to minimize artifacts due to sample handling. Other samples were deeply etched or were rewarmed to -20°C and recooled before replication. Yeast cells cooled at or above the rate necessary to preserve maximal viability (~7°C/min) contained intracellular ice, whereas cells cooled below this rate showed no evidence of intracellular ice. 相似文献