Autoimmune Responses Against Oxidant Stress and Acetaldehyde-Derived Epitopes in Human Alcohol Consumers

Viitala, Katja; Makkonen, Kati; Israel, Yedy; Lehtim??ki, Terho; Jaakkola, Olli; Koivula, Timo; Blake, Joan E.; Niemel??, Onni

doi:10.1097/00000374-200007000-00023

Cited by 18 publications

(21 citation statements)

References 31 publications

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“…Mitochondrial aldehyde dehydrogenases (ALDH2) then further catalyzes the production of acetate. Acetaldehyde is highly toxic; playing an important role in adduct formation, impairing hepatocyte secretory pathways (Thiele et al, 2008), contributing to immune responses (Viitala et al, 2000) and release of inflammatory cytokines (Tuma and Casey, 2003). Induction of the cytochrome P450 2E1 (CYP2E1) is also a key response to alcohol intake, resulting in an increased production of reactive oxidative species (ROS), mainly H 2 O 2 and superoxide anion (oxidative stress, Cederbaum, 2006).…”

Section: Discussionmentioning

confidence: 99%

Over expression of proteins that alter the intracellular signaling pathways in the cytoplasm of the liver cells forming Mallory-Denk bodies

Afifiyan

Tillman

French

et al. 2017

Experimental and Molecular Pathology

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In this study, liver biopsy sections fixed in formalin and embedded in paraffin (FFPE) from patients with alcoholic hepatitis (AH) were used. The results showed that the expression of the SYK protein was up regulated by RNA-seq and real time PCR analyses in the alcoholic hepatitis patients compared to controls. The results were supported by using the IHC fluorescent antibody staining intensity morphometric quantitation. Morphometric quantification of fluorescent intensity measurement showed a two fold increase in SYK protein in the cytoplasm of the cells forming MDBs compared to surrounding normal hepatocytes. The expression of AKT1 was also analyzed. AKT1 is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration. The AKT protein was also increased in hepatocyte balloon cells forming MDBs. This observation demonstrates the role of SYK and its subsequent effect on the internal signaling pathways such as PI3K/AKT as well as p70S6K, as a potential multifunctional target in protein quality control mechanisms of hepatocytes when ER stress is activated.

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Section: Discussionmentioning

confidence: 99%

Over expression of proteins that alter the intracellular signaling pathways in the cytoplasm of the liver cells forming Mallory-Denk bodies

Afifiyan

Tillman

French

et al. 2017

Experimental and Molecular Pathology

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“…Indeed, recent studies have shown that the titers of circulating IgG against epitopes derived from the binding of lipid peroxidation products to human albumin or low-density lipoproteins are significantly increased in patients with alcoholic liver disease. [23][24][25] Moreover, alcoholic patients also display a significant increase in antibodies that recognize oxidized cardiolipin (Ox-CL). 26…”

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confidence: 99%

Moderate Alcohol Consumption Increases Oxidative Stress in Patients With Chronic Hepatitis C

et al. 2003

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The mechanisms by which alcohol consumption worsens the evolution of chronic hepatitis C (CHC) are poorly understood. We have investigated the possible interaction between hepatitis C virus (HCV) and ethanol in promoting oxidative stress. Circulating IgG against human serum albumin (HSA) adducted with malondialdehyde (MDA-HSA), 4-hydroxynonenal (HNE-HSA), or arachidonic acid hydroperoxide (AAHP-HSA) and against oxidized cardiolipin (Ox-CL) were evaluated as markers of oxidative stress in 145 CHC patients with different alcohol consumption, 20 HCV-free heavy drinkers (HD) without liver disease, and 50 healthy controls. Anti-MDA IgG was increased in CHC patients irrespective of alcohol intake as well as in the HD group. CHC patients with moderate alcohol intake (<50 g ethanol/d), but not HD, also had significantly higher values of anti-AAHP-HSA, anti-HNE-HSA, and anti-Ox-CL IgG (P < .05) than controls. A further elevation (P < .001) of these antibodies was evident in CHC patients with heavy alcohol intake (>50 g ethanol/d). Anti-AAHP and anti-Ox-CL IgG above the 95th percentile in the controls were observed in 24% to 26% of moderate and 58% to 63% of heavy drinkers but only in 6% to 9% of the abstainers. The risk of developing oxidative stress during CHC was increased 3-fold by moderate and 13-to 24-fold by heavy alcohol consumption. Heavy drinking CHC patients had significantly more piecemeal necrosis and fibrosis than abstainers. Diffuse piecemeal necrosis was 4-fold more frequent among alcohol-consuming patients with lipid peroxidation-related antibodies than among those without these antibodies. In conclusion, even moderate alcohol consumption promotes oxidative stress in CHC patients, suggesting a role for oxidative injury in the worsening of CHC evolution by alcohol. (HEPATOLOGY 2003; 38:42-49.)

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“…While assays of more specific indicators of oxidative stress were beyond the scope of the present study, it should be noted that in previous studies, GGT has shown a correlation with 8-hydroxydeoxyguanosine (8-OHdG), acrolein-lysine adducts and aldehydic products of lipid peroxidation [34–37]. In humans, increased GGT levels have been reported in a wide variety of chronic diseases, and several lines of investigation have further emphasized the role of GGT as a risk marker for conditions involving oxidative stress, including cancer, neurodegenerative diseases, rheumatoid arthritis, atherosclerosis related events, fatty liver disease, diabetes and metabolic syndrome [12,13,38–46].…”

Section: Discussionmentioning

confidence: 99%

Individual and Joint Impacts of Ethanol Use, BMI, Age and Gender on Serum Gamma-Glutamyltransferase Levels in Healthy Volunteers

Danielsson

Kangastupa

Laatikainen

et al. 2013

IJMS

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Excessive ethanol consumption, obesity and increasing age may all lead to increased serum levels of gamma-glutamyltransferase (GGT) enzyme, which plays a key role in the metabolism of extracellular reduced glutathione. However, as yet, the interactions between the various modulators of GGT activities have remained poorly defined. We analyzed data from 15,617 apparently healthy individuals (7254 men and 8363 women, mean age 46 ± 13 years, range 25–74 years) who participated in a national cross-sectional health survey in Finland between 1997 and 2007. All subjects underwent detailed clinical examinations and interviews, including the amount of ethanol use and smoking habits. GGT levels were measured from all participants, and the individual and joint impacts of the different study variables on GGT levels were assessed. Significant individual effects were noted for ethanol use (p < 0.001), body mass index (BMI) (p < 0.001), age (p < 0.001) and smoking (p < 0.001). In men, significant two-factor interactions occurred between ethanol use and age (p < 0.020). Among those over 40 years of age, ethanol consumption was found to be a stronger determinant of increased GGT levels than in men below 40 years, whereas in the latter age group, BMI was found to predominate. In women, a significant two-factor interaction occurred between ethanol and BMI (p = 0.010), whereas it did not with ethanol use and age. The data underscores the role of ethanol consumption and age as major determinants of increased GGT levels in men, whereas in women, a relatively stronger impact was noted for ethanol intake and BMI. In light of the ability of GGT enzyme to modulate crucial redox-sensitive functions, the present findings also support the use of GGT as a biomarker of oxidative stress.

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Autoimmune Responses Against Oxidant Stress and Acetaldehyde-Derived Epitopes in Human Alcohol Consumers

Abstract: The present results indicated that autoantibodies against several distinct types of protein modifications are generated in ALD patients showing an association with the severity of liver disease.

Cited by 18 publications

References 31 publications

Over expression of proteins that alter the intracellular signaling pathways in the cytoplasm of the liver cells forming Mallory-Denk bodies

Over expression of proteins that alter the intracellular signaling pathways in the cytoplasm of the liver cells forming Mallory-Denk bodies

Moderate Alcohol Consumption Increases Oxidative Stress in Patients With Chronic Hepatitis C

Individual and Joint Impacts of Ethanol Use, BMI, Age and Gender on Serum Gamma-Glutamyltransferase Levels in Healthy Volunteers

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