Y James Kang

..These results thus demonstrate that zinc preservation of intestinal structural integrity is associated with suppression of endotoxemia and liver injury induced by acute exposure to ethanol and the zinc protection is independent of MT...

..The m-aconitase, not the cytosolic aconitase (c-aconitase), was co-immunoprecipitated with MT. This study demonstrates that MT transfers zinc to m-aconitase through a direct interaction...

..Overexpressing cardiac MT significantly protects the heart from diabetes-induced injury...

..Mice with cardiac myocyte-specific overexpression of Galphaq develop progressive left ventricular failure associated with myocyte contractile dysfunction and calcium dysregulation...

..The adaptation of new approaches such as functional genomics and proteomics will further advance our knowledge of heart hypertrophy...

..These results suggest that elevation in zinc but not in copper in the heart may be involved in the MT inhibition of copper deficiency-induced cardiac hypertrophy...

..In addition, MT posttranslationally modulates critical proteins involved in mitochondrial respiration and energy metabolism. All of these processes constitute the mechanisms by which MT protects from anthracycline cardiotoxicity...

..This process thus establishes a herbogenomics approach to understand mechanisms of action of TCM and to identify effective molecular targets for the discovery and development of novel therapeutics...

..Zn has a high potential to be developed as an effective agent in the prevention and treatment of ALD...

..Most of these changes are recoverable upon withdrawal of the toxic insult. However, liver fibrosis is a prolonged change both in gene expression and histopathological alterations...

..A comprehensive understanding of Cu speciation and a development of selective modulation of Cu coordination to Cu-binding molecules to avoid Cu-Hcy complex formation would effectively improve the condition of cardiovascular disease...

..This MT redox cycle may play a crucial role in MT biologic function. It may link to the homeostasis of essential metals, detoxification of toxic metals and protection against oxidative stress...

..In conclusion, zinc supplementation prevents alcoholic liver injury in an metallothionein-independent manner by inhibiting the generation of reactive oxygen species (P450 2E1) and enhancing the activity of antioxidant pathways...

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..We aimed to test whether attenuation of early-phase cardiac cell death can prevent diabetic cardiomyopathy...

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..Thus, zinc may be beneficial in the treatment of LPS-induced liver injuries, such as sepsis and alcoholism...

..5 or 3.0 mg Cu/kg diet. These results demonstrate that, in the absence of most indications of systemic Cu deficiency, heart morphology and function are sensitive to marginal Cu deficiency...

..These results suggest that zinc protects against TNF-alpha hepatotoxicity, at least partially, through preservation of the zinc finger protein HNF-4alpha...

..Additional zinc release from MT under oxidative stress conditions is accompanied by more MT disulfide bond formation...

..In conclusion, our data suggest that copper supplement helps improve cardiac function in a pressure overload dilated cardiomyopathic heart...

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..Therefore, elevation of HIF-1alpha provides a cardiac protection from diabetic-induced impairment in glucose metabolism and angiogenesis via up-regulation of HIF-1 target genes...

..A rapid decrease in mitochondrial GSH content may be partially responsible for the observed mitochondrial damage...

..The antiapoptotic effect of MT likely results from the suppression of oxidative stress and correlates with the inhibition of myocardial infarction...

..These data further support improving the S-adenosylmethionine-to-SAH ratio and removal of intracellular SAH as potential therapeutic options in alcoholic liver disease...

..In conclusion, zinc supplementation prevented hepatocyte apoptosis in mice subjected to long-term ethanol exposure, and the action of zinc is likely through suppression of oxidative stress and death receptor-mediated pathways...

..This study demonstrates that both Cu and VEGF can restore COX activity that is depressed in hypertrophic cardiomyocytes, and COX plays a determinant role in both Cu- and VEGF-induced regression of cardiomyocyte hypertrophy...

..This study thus defines that copper is required for HIF-1 activation through the regulation of HIF-1alpha binding to the HRE and the formation of the HIF-1 transcriptional complex...

..These results demonstrate that zinc is a potent inhibitor of acute ethanol-induced liver apoptosis, and this effect occurs primarily through zinc interference with Fas ligand pathway and the suppression of caspase-3...

..These results thus suggest that metallothionein prevention of diabetic cardiomyopathy is mediated, at least in part, by suppression of superoxide generation and associated nitrosative damage...

..This study shows that CuD leads to systolic and diastolic dysfunction in association with histopathological changes, which are indices commonly used to diagnose congestive heart failure...

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..This model would also provide an excellent tool for drug discovery and development for cardiac disease...

..2 microg/ml reversed cell hypertrophy as the same as copper did. This study demonstrates that both copper and VEGF reduce the size of hypertrophied cardiomyocytes, and copper regression of cardiac hypertrophy is VEGF-dependent...

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..It had been shown previously that calcineurin is also not necessary for DOX-induced H9c2 cell hypertrophy.)...

..Because CCO-Va is a critical component in the mitochondrial electron transport chain, the results suggest that the cardioprotective effect of MT may be related to an increased expression or a differential modification of CCO-Va...

..These results suggest that diabetes significantly enhances endotoxin-induced cardiac toxicity, possibly through mechanisms that involve inflammatory/acute-phase cytokines...

..This study thus suggests that p38 MAPK activation is likely involved in TNFinduced cardiomyocyte apoptosis, which is also related to reactive oxygen species accumulation...

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..Therefore, dietary Cu supplementation improves the condition of hypertrophic cardiomyopathy at least in part through CCS-mediated HIF-1alpha activation of VEGF expression and angiogenesis...

..The present study thus demonstrates that copper was required for cobalt-activated transcriptional activity of HIF-1, although copper did not affect cobalt-induced accumulation of HIF-1α in the cells...

..The expression of TIMP1 was not changed. The data thus demonstrated that the collagen deposition in infarcted myocardium is correlated with an enhanced cross-linking capacity and a decreased degradation process...

..However, siRNA targeting eNOS completely blocked Cu reversal of TEPA inhibition of cell growth. The data demonstrate that Cu stimulation of HUVEC cell growth is VEGF-independent, but eNOS-dependent...

..These results thus demonstrate that zinc prevention of increased intestinal permeability is importantly involved in the inhibition of acute ethanol-induced liver damage in mice...

..Our study thus demonstrates that arsenic trioxide, in a dose that could produce clinically comparable serum concentrations to those observed in humans, causes cardiotoxicity...

..This study indicates that MT makes a critical contribution to the reversal of chemical-induced hepatic fibrosis and has therapeutic potential for patients with certain liver fibrosis...

..However, MT is required to maintain high levels of zinc in the liver, suggesting that the protective action of MT in the liver is likely mediated by zinc...

..Rather, the PI3K-Akt signaling pathway seems to be more critically involved in DOX-induced hypertrophy...

..The return to normal cardiac function by CuR may be a result of the favorable regression in gene expression of these critical components in myocardial tissue...

..In conclusion, inactivation of HDAC caused by zinc deprivation is a novel mechanism underlying IL-8 up-regulation in alcoholic hepatitis...

..The addition of MT into the cultures of H9c2 cells relieved the HG suppression of hypoxia-induced luciferase activity. This study indicates that MT can rescue HIF-1 transcriptional activity in cardiomyocytes under diabetic conditions...

..However, MT can protect the heart from oxidative injury only if it is present prior to induction of oxidative stress...

..This study thus suggests that upregulation of the endothelin system in rats with MI is likely involved in the PM exposure-induced cardiotoxicity...

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..In this context, a development of diagnosis for copper metabolic changes as well as a tissue-specific copper manipulation would greatly benefit patients with an implication of copper manipulation therapy...

..The signal transduction mechanisms in Hcy-induced matrix metalloproteinase (MMP) activation in cardiac connexin remodeling are discussed...

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..This study thus suggests that MT may contribute to cytoprotection, thereby inhibiting apoptosis and leading to carcinogenesis of Barrett's esophageal cells...

..More exciting insights into the regression of pathological cardiac hypertrophy are emerging. The time of translating the concept of regression of pathological cardiac hypertrophy to clinical practice is coming...

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..The results thus demonstrated that VEGF is critically involved in copper inhibition of cell hypertrophy induced by hydrogen peroxide in the H9c2 cells...

..Novel approaches, such as functional genomics, proteomics and metabonomics, should significantly improve our understanding of cardiotoxicity...

..Hyperglycemia-induced myocardial apoptosis is mediated, at least in part, by activation of the cytochrome c-activated caspase-3 pathway, which may be triggered by ROS derived from high levels of glucose...

..The results indicate that catalase elevation in the heart prevents doxorubicin chronic cardiomyopathy...

..Together, these results illustrate that formation of a signaling module between PKCepsilon and Src involves specific domains within the two molecules and is governed by the molecular conformation of PKCepsilon...

..Several studies have suggested a defective liver regeneration after an injury in MT-knockout mice. There is cumulative evidence that indicates an essential role for MT in liver cell regeneration...

..Thus reducing the number of intestinal Gram-negative bacteria and preserving intestinal permeability to endotoxin may attenuate alcoholic liver and other organ injuries...

..abstract_text> ..

..Therefore, Cu supplementation is not an appropriate approach to rescue diabetic cardiomyopathy. ..

..Therefore, Cu supplementation is not an appropriate approach to rescue diabetic cardiomyopathy. ..

..Importantly, the data obtained will provide valuable information for novel experimental as well as clinical approaches for possible interventions of the transition from heart hypertrophy to heart failure. ..

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