Protective effect of Aplysin on hepatic injury in ethanol-treated rats

Ge, Na; Liang, Hui; Liu, Ying; Ma, Aiguo; Han, Li

doi:10.1016/j.fct.2013.08.071

Cited by 24 publications

(27 citation statements)

References 57 publications

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“…(Wheeler et al, 2001). However, another study conducted by Ge et al reported that ethanol metabolism significantly decreased SOD2 activity (Ge et al, 2013) and Roede et al demonstrated similar findings, in agreement with our findings (Roede et al, 2009). In aggregate, it is apparent that examining SOD2 activity in varying models of alcohol is complicated and further studies are needed to reveal the underlying mechanisms of how ethanol metabolism and resulting epiproteomic alterations regulate SOD2 activity.…”

Section: Discussionsupporting

confidence: 93%

Chronic Ethanol Metabolism Inhibits Hepatic Mitochondrial Superoxide Dismutase via Lysine Acetylation

Assiri

Roy

Harris

et al. 2017

Alcohol Clin Exp Res

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Background Chronic ethanol consumption is a major cause of liver disease worldwide. Oxidative stress is a known consequence of ethanol metabolism and is thought to contribute significantly to alcoholic liver disease (ALD). Therefore, elucidating pathways leading to sustained oxidative stress and downstream redox imbalances may reveal how ethanol consumption leads to ALD. Recent studies suggest that ethanol metabolism impacts mitochondrial antioxidant processes through a number of proteomic alterations, including hyperacetylation of key antioxidant proteins. Methods In order to elucidate mechanisms of ethanol-induced hepatic oxidative stress, we investigate a role for protein hyperacetylation in modulating mitochondrial superoxide dismutase (SOD2) structure and function in a 6-week Lieber-DeCarli murine model of ethanol consumption. Our experimental approach includes immunoblotting, immunohistochemistry, activity assays, mass spectrometry, and in silico modeling. Results We found that ethanol metabolism significantly increased the acetylation of SOD2 at two functionally relevant lysine sites, K68 and K122, resulting in a 40% decrease in enzyme activity while overall SOD2 abundance was unchanged. In vitro studies also reveal which lysine residues are more susceptible to acetylation. Immunohistochemical analysis demonstrates that SOD2 hyperacetylation occurs near zone 3 within the liver, which is the main ethanol-metabolizing region of the liver. Conclusion Overall, the findings presented in this study support a role for ethanol-induced lysine acetylation as an adverse post-translational modification within the mitochondria that directly impacts SOD2 charge-state and activity. Lastly, the data presented here indicate that protein hyperacetylation may be a major factor contributing to an imbalance in hepatic redox homeostasis due to chronic ethanol metabolism.

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Section: Discussionsupporting

confidence: 93%

Chronic Ethanol Metabolism Inhibits Hepatic Mitochondrial Superoxide Dismutase via Lysine Acetylation

Assiri

Roy

Harris

et al. 2017

Alcohol Clin Exp Res

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“…In addition, increased ratio of NADH/NAD + is also suggested to contribute to the pathogenesis of fatty liver in part by modulating fatty acid metabolism [38]. In our experiment, NADH/NAD + ratio were increased in alcohol group consistent with other studies [35, 36], besides, we found iron overload further facilitated the NADH/NAD + ratio. High level of NADH was found to facilitate the formation of H 2 O 2 , and the existence of iron would catalyze the generation of free radicals through Fenton reaction [10].…”

Section: Discussionsupporting

confidence: 91%

Synergistic Interaction of Light Alcohol Administration in the Presence of Mild Iron Overload in a Mouse Model of Liver Injury: Involvement of Triosephosphate Isomerase Nitration and Inactivation

Gao¹,

Zhao²,

Gao³

et al. 2017

PLoS ONE

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It is well known that iron overload promotes alcoholic liver injury, but the doses of iron or alcohol used in studies are usually able to induce liver injury independently. Little attention has been paid to the coexistence of low alcohol consumption and mild iron overload when either of them is insufficient to cause obvious liver damage, although this situation is very common among some people. We studied the interactive effects and the underlining mechanism of mild doses of iron and alcohol on liver injury in a mouse model. Forty eight male Kunming mice were randomly divided into four groups: control, iron (300 mg/kg iron dextran, i.p.), alcohol (2 g/kg/day ethanol for four weeks i.g.), and iron plus alcohol group. After 4 weeks of treatment, mice were sacrificed and blood and livers were collected for biochemical analysis. Protein nitration level in liver tissue was determined by immunoprecipitation and Western blot analysis. Although neither iron overload nor alcohol consumption at our tested doses can cause severe liver injury, it was found that co-administration of the same doses of alcohol and iron resulted in liver injury and hepatic dysfunction, accompanied with elevated ratio of NADH/NAD+, reduced antioxidant ability, increased oxidative stress, and subsequent elevated protein nitration level. Further study revealed that triosephosphate isomerase, an important glycolytic enzyme, was one of the targets to be oxidized and nitrated, which was responsible for its inactivation. These data indicate that even under low alcohol intake, a certain amount of iron overload can cause significant liver oxidative damage, and the modification of triosephosphate isomerasemight be the important underlining mechanism of hepatic dysfunction.

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“…Aplysin (195) has shown a protective effect on hepatic injury induced by ethanol in rats [893]. The triquinanes 490 and 492 exhibited weak antioxidant activity when evaluated in the DPPH radical-scavenging assay [458].…”

Section: Miscellaneous Biological Activitiesmentioning

confidence: 99%

The Laurencia Paradox: An Endless Source of Chemodiversity

Harizani

Iοannou

Roussis

2016

Progress in the Chemistry of Organic Natural Products 102

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Nature, the most prolific source of biological and chemical diversity, has provided mankind with treatments for health problems since ancient times and continues to be the most promising reservoir of bioactive chemicals for the development of modern drugs. In addition to the terrestrial organisms that still remain a promising source of new bioactive metabolites, the marine environment, covering approximately 70% of the Earth's surface and containing a largely unexplored biodiversity, offers an enormous resource for the discovery of novel compounds. According to the MarinLit database, more than 27,000 metabolites from marine macro- and microorganisms have been isolated to date providing material and key structures for the development of new products in the pharmaceutical, food, cosmeceutical, chemical, and agrochemical sectors. Algae, which thrive in the euphotic zone, were among the first marine organisms that were investigated as sources of food, nutritional supplements, soil fertilizers, and bioactive metabolites.Red algae of the genus Laurencia are accepted unanimously as one of the richest sources of new secondary metabolites. Their cosmopolitan distribution, along with the chemical variation influenced to a significant degree by environmental and genetic factors, have resulted in an endless parade of metabolites, often featuring multiple halogenation sites.The present contribution, covering the literature until August 2015, offers a comprehensive view of the chemical wealth and the taxonomic problems currently impeding chemical and biological investigations of the genus Laurencia. Since mollusks feeding on Laurencia are, in many cases, bioaccumulating, and utilize algal metabolites as chemical weaponry against natural enemies, metabolites of postulated dietary origin of sea hares that feed on Laurencia species are also included in the present review. Altogether, 1047 secondary metabolites, often featuring new carbocyclic skeletons, have been included.The chapter addresses: (1) the "Laurencia complex", the botanical description and the growth and population dynamics of the genus, as well as its chemical diversity and ecological relations; (2) the secondary metabolites, which are organized according to their chemical structures and are classified into sesquiterpenes, diterpenes, triterpenes, acetogenins, indoles, aromatic compounds, steroids, and miscellaneous compounds, as well as their sources of isolation which are depicted in tabulated form, and (3) the biological activity organized according to the biological target and the ecological functions of Laurencia metabolites.

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Protective effect of Aplysin on hepatic injury in ethanol-treated rats

Cited by 24 publications

References 57 publications

Chronic Ethanol Metabolism Inhibits Hepatic Mitochondrial Superoxide Dismutase via Lysine Acetylation

Chronic Ethanol Metabolism Inhibits Hepatic Mitochondrial Superoxide Dismutase via Lysine Acetylation

Synergistic Interaction of Light Alcohol Administration in the Presence of Mild Iron Overload in a Mouse Model of Liver Injury: Involvement of Triosephosphate Isomerase Nitration and Inactivation

The Laurencia Paradox: An Endless Source of Chemodiversity

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