The Experts below are selected from a list of 17046 Experts worldwide ranked by ideXlab platform
Jae H. Park - One of the best experts on this subject based on the ideXlab platform.
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regulation of Ethanol related behavior and Ethanol Metabolism by the corazonin neurons and corazonin receptor in drosophila melanogaster
PLOS ONE, 2014Co-Authors: Seunghoon Choi, Frank Loeffler, Jeongdae Im, Jae H. ParkAbstract:Impaired Ethanol Metabolism can lead to various alcohol-related health problems. Key enzymes in Ethanol Metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH); however, neuroendocrine pathways that regulate the activities of these enzymes are largely unexplored. Here we identified a neuroendocrine system involving Corazonin (Crz) neuropeptide and its receptor (CrzR) as important physiological regulators of Ethanol Metabolism in Drosophila. Crz-cell deficient (Crz-CD) flies displayed significantly delayed recovery from Ethanol-induced sedation that we refer to as hangover-like phenotype. Newly generated mutant lacking Crz Receptor (CrzR01) and CrzR-knockdown flies showed even more severe hangover-like phenotype, which is causally associated with fast accumulation of acetaldehyde in the CrzR01 mutant following Ethanol exposure. Higher levels of acetaldehyde are likely due to 30% reduced ALDH activity in the mutants. Moreover, increased ADH activity was found in the CrzR01 mutant, but not in the Crz-CD flies. Quantitative RT-PCR revealed transcriptional upregulation of Adh gene in the CrzR01. Transgenic inhibition of cyclic AMP-dependent protein kinase (PKA) also results in significantly increased ADH activity and Adh mRNA levels, indicating PKA-dependent transcriptional regulation of Adh by CrzR. Furthermore, inhibition of PKA or cAMP response element binding protein (CREB) in CrzR cells leads to comparable hangover-like phenotype to the CrzR01 mutant. These findings suggest that CrzR-associated signaling pathway is critical for Ethanol detoxification via Crz-dependent regulation of ALDH activity and Crz-independent transcriptional regulation of ADH. Our study provides new insights into the neuroendocrine-associated Ethanol-related behavior and Metabolism.
Michael Laposata - One of the best experts on this subject based on the ideXlab platform.
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Linkage of oxidative and nonoxidative Ethanol Metabolism in the pancreas and toxicity of nonoxidative Ethanol metabolites for pancreatic acinar cells.
Surgery, 2001Co-Authors: Jens Werner, Mouris Saghir, Carlos Fernandez-del Castillo, Andrew L. Warshaw, Michael LaposataAbstract:Abstract Background. Alcohol abuse is a major cause of pancreatic damage. Recent experimental evidence suggests that fatty acid ethyl esters (FAEE), nonoxidative Ethanol metabolites, injure pancreatic acinar cells. Linkage between oxidative and nonoxidative Metabolism of Ethanol in the pancreas may contribute to increased FAEE levels. Methods. To study the association between oxidative and nonoxidative Ethanol Metabolism, FAEE concentration and FAEE synthase activity in rat pancreatic and liver homogenates incubated with Ethanol were evaluated with and without inhibitors of oxidative Ethanol Metabolism. For toxicity studies, trypsinogen activation peptide synthesis as a measure of pancreatic cell injury was quantitated in unstimulated and cerulein-stimulated isolated pancreatic acinar cells incubated with Ethanol or FAEE. Results. Inhibition of oxidative Ethanol Metabolism results in a 2- to 3-fold increase in nonoxidative Ethanol Metabolism to FAEE in pancreas and in liver. Both Ethanol and FAEE induce increased intracellular trypsinogen activation by more than 50% in the presence of physiologic concentrations of cerulein in vitro. Conclusions. These findings demonstrate that the inhibition of oxidative Ethanol Metabolism results in an increase in flux through the nonoxidative pathway and support the proposition that alcohol-induced pancreatic injury is mediated at least in part by FAEE, which are important products of pancreatic Ethanol Metabolism.(Surgery 2001;129:736-44.)
Seunghoon Choi - One of the best experts on this subject based on the ideXlab platform.
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regulation of Ethanol related behavior and Ethanol Metabolism by the corazonin neurons and corazonin receptor in drosophila melanogaster
PLOS ONE, 2014Co-Authors: Seunghoon Choi, Frank Loeffler, Jeongdae Im, Jae H. ParkAbstract:Impaired Ethanol Metabolism can lead to various alcohol-related health problems. Key enzymes in Ethanol Metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH); however, neuroendocrine pathways that regulate the activities of these enzymes are largely unexplored. Here we identified a neuroendocrine system involving Corazonin (Crz) neuropeptide and its receptor (CrzR) as important physiological regulators of Ethanol Metabolism in Drosophila. Crz-cell deficient (Crz-CD) flies displayed significantly delayed recovery from Ethanol-induced sedation that we refer to as hangover-like phenotype. Newly generated mutant lacking Crz Receptor (CrzR01) and CrzR-knockdown flies showed even more severe hangover-like phenotype, which is causally associated with fast accumulation of acetaldehyde in the CrzR01 mutant following Ethanol exposure. Higher levels of acetaldehyde are likely due to 30% reduced ALDH activity in the mutants. Moreover, increased ADH activity was found in the CrzR01 mutant, but not in the Crz-CD flies. Quantitative RT-PCR revealed transcriptional upregulation of Adh gene in the CrzR01. Transgenic inhibition of cyclic AMP-dependent protein kinase (PKA) also results in significantly increased ADH activity and Adh mRNA levels, indicating PKA-dependent transcriptional regulation of Adh by CrzR. Furthermore, inhibition of PKA or cAMP response element binding protein (CREB) in CrzR cells leads to comparable hangover-like phenotype to the CrzR01 mutant. These findings suggest that CrzR-associated signaling pathway is critical for Ethanol detoxification via Crz-dependent regulation of ALDH activity and Crz-independent transcriptional regulation of ADH. Our study provides new insights into the neuroendocrine-associated Ethanol-related behavior and Metabolism.
Stephen J. Pandol - One of the best experts on this subject based on the ideXlab platform.
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Ethanol Metabolism and transcription factor activation in pancreatic acinar cells in rats.
Gastroenterology, 2002Co-Authors: Anna S. Gukovskaya, Michelle Mouria, Ilya Gukovsky, Christopher N. Reyes, Vladimir N. Kasho, Larry D. Faller, Stephen J. PandolAbstract:Abstract Background & Aims: Ethanol Metabolism by pancreatic acinar cells and the role of its metabolites in Ethanol toxicity to the pancreas remain largely unknown. Here, we characterize Ethanol Metabolism in pancreatic acinar cells and determine the effects of Ethanol metabolites on nuclear factor κB (NF-κB) and activator protein (AP)-1, transcription factors that are activated in pancreatitis and mediate expression of inflammatory molecules critical for this disease. Methods: We measured activities of fatty acid ethyl ester (FAEE) synthase and alcohol dehydrogenase (ADH), as well as accumulation of Ethanol metabolites. We measured the effects of Ethanol and its metabolites on NF-κB and AP-1 activation by using a gel shift assay. Results: Pancreas metabolizes Ethanol via both oxidative and nonoxidative pathways. Acinar cells are the main source of Ethanol Metabolism in the pancreas. Compared with the liver, FAEE synthase activity in the pancreas is greater, whereas that of ADH is much less. FAEEs activated NF-κB and AP-1, whereas acetaldehyde inhibited NF-κB activation. Ethanol decreased NF-κB binding activity in acinar cells, which was potentiated by cyanamide. Conclusion: Oxidative and nonoxidative Ethanol metabolites regulate transcription factors differently in pancreatic acinar cells. Ethanol may regulate NF-κB and AP-1 positively or negatively, depending on which metabolic pathway's effect predominates. These regulatory mechanisms may play a role in Ethanol toxicity to the pancreas. GASTROENTEROLOGY 2002;122:106-118
Jens Werner - One of the best experts on this subject based on the ideXlab platform.
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Linkage of oxidative and nonoxidative Ethanol Metabolism in the pancreas and toxicity of nonoxidative Ethanol metabolites for pancreatic acinar cells.
Surgery, 2001Co-Authors: Jens Werner, Mouris Saghir, Carlos Fernandez-del Castillo, Andrew L. Warshaw, Michael LaposataAbstract:Abstract Background. Alcohol abuse is a major cause of pancreatic damage. Recent experimental evidence suggests that fatty acid ethyl esters (FAEE), nonoxidative Ethanol metabolites, injure pancreatic acinar cells. Linkage between oxidative and nonoxidative Metabolism of Ethanol in the pancreas may contribute to increased FAEE levels. Methods. To study the association between oxidative and nonoxidative Ethanol Metabolism, FAEE concentration and FAEE synthase activity in rat pancreatic and liver homogenates incubated with Ethanol were evaluated with and without inhibitors of oxidative Ethanol Metabolism. For toxicity studies, trypsinogen activation peptide synthesis as a measure of pancreatic cell injury was quantitated in unstimulated and cerulein-stimulated isolated pancreatic acinar cells incubated with Ethanol or FAEE. Results. Inhibition of oxidative Ethanol Metabolism results in a 2- to 3-fold increase in nonoxidative Ethanol Metabolism to FAEE in pancreas and in liver. Both Ethanol and FAEE induce increased intracellular trypsinogen activation by more than 50% in the presence of physiologic concentrations of cerulein in vitro. Conclusions. These findings demonstrate that the inhibition of oxidative Ethanol Metabolism results in an increase in flux through the nonoxidative pathway and support the proposition that alcohol-induced pancreatic injury is mediated at least in part by FAEE, which are important products of pancreatic Ethanol Metabolism.(Surgery 2001;129:736-44.)