Dataset Information

3, 4-dihydroxyl-phenyl lactic acid restores NADH dehydrogenase 1 ? subunit 10 to ameliorate cardiac reperfusion injury.

ABSTRACT: The present study aimed to detect the role of 3, 4-dihydroxyl-phenyl lactic acid (DLA) during ischemia/reperfusion (I/R) induced myocardial injury with emphasis on the underlying mechanism of DLA antioxidant. Male Spragu-Dawley (SD) rats were subjected to left descending artery occlusion followed by reperfusion. Treatment with DLA ameliorated myocardial structure and function disorder, blunted the impairment of Complex I activity and mitochondrial function after I/R. The results of 2-D fluorescence difference gel electrophoresis revealed that DLA prevented the decrease in NDUFA10 expression, one of the subunits of Complex I. To find the target of DLA, the binding affinity of Sirtuin 1 (SIRT1) to DLA and DLA derivatives with replaced two phenolic hydroxyls was detected using surface plasmon resonance and bilayer interferometry. The results showed that DLA could activate SIRT1 after I/R probably by binding to this protein, depending on phenolic hydroxyl. Moreover, the importance of SIRT1 to DLA effectiveness was confirmed through siRNA transfection in vitro. These results demonstrated that DLA was able to prevent I/R induced decrease in NDUFA10 expression, improve Complex I activity and mitochondrial function, eventually attenuate cardiac structure and function injury after I/R, which was possibly related to its ability of binding to and activating SIRT1.

SUBMITTER: Yang XY

PROVIDER: S-EPMC5377067 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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3, 4-dihydroxyl-phenyl lactic acid restores NADH dehydrogenase 1 α subunit 10 to ameliorate cardiac reperfusion injury.

Yang Xiao-Yuan XY He Ke K Pan Chun-Shui CS Li Quan Q Liu Yu-Ying YY Yan Li L Wei Xiao-Hong XH Hu Bai-He BH Chang Xin X Mao Xiao-Wei XW Huang Dan-Dan DD Wang Li-Jun LJ Hu Shui-Wang SW Jiang Yong Y Wang Guo-Cheng GC Fan Jing-Yu JY Fan Tai-Ping TP Han Jing-Yan JY

Scientific reports 20150601

The present study aimed to detect the role of 3, 4-dihydroxyl-phenyl lactic acid (DLA) during ischemia/reperfusion (I/R) induced myocardial injury with emphasis on the underlying mechanism of DLA antioxidant. Male Spragu-Dawley (SD) rats were subjected to left descending artery occlusion followed by reperfusion. Treatment with DLA ameliorated myocardial structure and function disorder, blunted the impairment of Complex I activity and mitochondrial function after I/R. The results of 2-D fluoresce ...[more]

PMID: 26030156

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Project description:Accumulating evidence indicates that mitochondrial DNA alterations contribute to cancer development and progression. In this study, we evaluated the relationship between polymorphisms of mitochondrial NADH dehydrogenase subunit 3 (MTND3) and the risk of gastric cancer (GC). Five single nucleotide polymorphisms (SNPs; rs28358278, rs2853826, rs201397417, rs41467651, and rs28358275) were identified and genotyped in 377 patients with GC patients and 363 controls by direct sequencing. The rs41467651 T allele was significantly associated with GC risk [adjusted odds ratio (OR) = 2.11, 95% confidence interval (CI) = 1.25-3.55, P = 0.005). In stratified analysis, rs28358278, rs2853826, and rs41467651 were associated with subgroups of GC, with the rs28358278 G, rs2853826 T, and rs41467651 T alleles associated with an increased GC risk in females (adjusted OR = 1.70, 95% CI = 1.08-2.69, P = 0.023; adjusted OR = 1.78, 95% CI = 1.11-2.85, P = 0.016; adjusted OR = 2.07, 95% CI = 1.04-4.12, P = 0.038, respectively). The rs441467651 T allele was also related with GC risk in diffuse-type subjects compared to that of controls (adjusted OR = 2.61, 95% CI = 1.43-4.89, P = 0.002). In addition, The rs441467651 T allele was significantly related with increased GC risk regardless of lymph node metastasis (LNM), T classification, and tumor stage compared to that of controls (adjusted OR = 2.00, 95% CI = 1.12-3.55, P = 0.019 in LNM-negative subjects; adjusted OR = 2.10, 95% CI = 1.05-4.22, P = 0.0379 in LNM-positive subjects; adjusted OR = 1.82, 95% CI = 1.02-3.24, P = 0.042 in T1/T2 subjects; adjusted OR = 2.60, 95% CI = 1.29-5.24, P = 0.007 in T3/T4 subjects; adjusted OR = 1.91, 95% CI = 1.09-3.34, P = 0.025 in tumor stage I (A+B)/II (A+B+C) subjects; adjusted OR = 2.36, 95% CI = 1.12-5.13, P = 0.025 in tumor stage III (A+B+C) subjects) compared to that of controls. Our findings suggest that the rs28358278, rs2853826, and rs41467651 polymorphisms of MTND3 increase the susceptibility to GC development.

Project description:BackgroundDuring and following myocardial ischemia, glucose oxidation rates are low and fatty acids dominate as a source of oxidative metabolism. This metabolic phenotype is associated with contractile dysfunction during reperfusion. To determine the mechanism of this reliance on fatty acid oxidation as a source of ATP generation, a functional proteomics approach was utilized.Results2-D gel electrophoresis of mitochondria from working rat hearts subjected to 25 minutes of global no flow ischemia followed by 40 minutes of aerobic reperfusion identified 32 changes in protein abundance compared to aerobic controls. Of the five proteins with the greatest change in abundance, two were increased (long chain acyl-coenzyme A dehydrogenase (48 +/- 1 versus 39 +/- 3 arbitrary units, n = 3, P < 0.05) and alpha subunit of ATP synthase (189 +/- 15 versus 113 +/- 23 arbitrary units, n = 3, P < 0.05)), while two were decreased (24 kDa subunit of NADH-ubiquinone oxidoreductase (94 +/- 7 versus 127 +/- 9 arbitrary units, n = 3, P < 0.05) and D subunit of ATP synthase (230 +/- 11 versus 368 +/- 47 arbitrary units, n = 3, P < 05)). Two forms of pyruvate dehydrogenase betaE1 subunit, the rate-limiting enzyme for glucose oxidation, were also identified. The protein level of the more acidic form of pyruvate dehydrogenase was reduced during reperfusion (37 +/- 4 versus 56 +/- 7 arbitrary units, n = 3, P < 05), while the more basic form remained unchanged. The more acidic isoform was found to be O-palmitoylated, while both isoforms exhibited ischemia/reperfusion-induced phosphorylation. In silico analysis identified the putative kinases as the insulin receptor kinase for the more basic form and protein kinase Czeta or protein kinase A for the more acidic form. These modifications of pyruvate dehydrogenase are associated with a 35% decrease in glucose oxidation during reperfusion.ConclusionsCardiac ischemia/reperfusion induces significant changes to a number of metabolic proteins of the mitochondrial proteome. In particular, ischemia/reperfusion induced the post-translational modification of pyruvate dehydrogenase, the rate-limiting step of glucose oxidation, which is associated with a 35% decrease in glucose oxidation during reperfusion. Therefore these post-translational modifications may have important implications in the regulation of myocardial energy metabolism.

Dataset Information

3, 4-dihydroxyl-phenyl lactic acid restores NADH dehydrogenase 1 ? subunit 10 to ameliorate cardiac reperfusion injury.

Publications

3, 4-dihydroxyl-phenyl lactic acid restores NADH dehydrogenase 1 α subunit 10 to ameliorate cardiac reperfusion injury.

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