Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum antibodies reactive with neo-antigens generated during ethanol metabolism have been identified in patients with alcoholic liver disease (ALD), although their role in the pathogenesis of disease remains unclear. In this study, we characterized peripheral blood mononuclear cell (PBMC) T-cell and antibody responses to human serum albumin (HAS) adducted with acetaldehyde under reducing conditions (AcA-HSA) or with malondialdehyde (MDA-HSA) in patients with advanced ALD (AALD, n = 28), heavy drinkers with no liver disease (NALD, n = 14), and mild/moderate drinking controls (n = 22). Peak proliferative responses of PBMC were assessed in vitro by tritiated thymidine incorporation after the addition of optimized concentrations of antigen or OKT3. Antibody titers were determined by enzyme-linked immunosorbent assay (ELISA). MDA-HSA induced PBMC T-cell proliferation was significantly higher in ALD than in NALD or control patients. Moreover, 10 of 28 (36%) of ALD patients had significant T-cell proliferative responses to MDA-HSA compared to 0 of 14 (0%, P =.02) of the NALD group and 2 of 22 (9%, P <.05) of controls. No significant difference in PBMC T-cell response to Aca-HSA was seen between subject groups. Patients with positive cellular responses to MDA had higher serum anti-MDA antibody titers than those not exhibiting a positive cellular response (P <.005). In conclusion, the pattern of cellular and humoral responses to MDA adducts suggests that the development of these responses may be a susceptibility factor for the development of advanced alcoholic liver disease. The apparent importance of T-cell responses to MDA adducts suggests that oxidative stress may represent an important stimulus for the development of cellular immune responses associated with advanced ALD.
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PMID:Oxidative stress as a trigger for cellular immune responses in patients with alcoholic liver disease. 1475 38

Malondialdehyde-acetaldehyde adducts (MAA) have been implicated in atherosclerosis. The purpose of this study was to investigate the role of MAA in atherosclerotic disease. Serum samples from controls (n = 82) and patients with; non-obstructive coronary artery disease (CAD), (n = 40), acute myocardial infarction (AMI) (n = 42), or coronary artery bypass graft (CABG) surgery due to obstructive multi-vessel CAD (n = 72), were collected and tested for antibody isotypes to MAA-modifed human serum albumin (MAA-HSA). CAD patients had elevated relative levels of IgG and IgA anti-MAA, compared to control patients (p<0.001). AMI patients had a significantly increased relative levels of circulating IgG anti-MAA-HSA antibodies as compared to stable angina (p<0.03) or CABG patients (p<0.003). CABG patients had significantly increased relative levels of circulating IgA anti-MAA-HSA antibodies as compared to non-obstructive CAD (p<0.001) and AMI patients (p<0.001). Additionally, MAA-modified proteins were detected in the tissue of human AMI lesions. In conclusion, the IgM, IgG and IgA anti-MAA-HSA antibody isotypes are differentially and significantly associated with non-obstructive CAD, AMI, or obstructive multi-vessel CAD and may serve as biomarkers of atherosclerotic disease.
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PMID:Unique antibody responses to malondialdehyde-acetaldehyde (MAA)-protein adducts predict coronary artery disease. 2521 Jul 46

Staphylococcus aureus produces bacillithiol (BSH) as major low molecular weight (LMW) thiol which functions in thiol-protection and redox-regulation by protein S-bacillithiolation under hypochlorite stress. The aldehyde dehydrogenase AldA was identified as S-bacillithiolated at its active site Cys279 under NaOCl stress in S. aureus. Here, we have studied the expression, function, redox regulation and structural changes of AldA of S. aureus. Transcription of aldA was previously shown to be regulated by the alternative sigma factor SigmaB. Northern blot analysis revealed SigmaB-independent induction of aldA transcription under formaldehyde, methylglyoxal, diamide and NaOCl stress. Deletion of aldA resulted in a NaOCl-sensitive phenotype in survival assays, suggesting an important role of AldA in the NaOCl stress defense. Purified AldA showed broad substrate specificity for oxidation of several aldehydes, including formaldehyde, methylglyoxal, acetaldehyde and glycol aldehyde. Thus, AldA could be involved in detoxification of aldehyde substrates that are elevated under NaOCl stress. Kinetic activity assays revealed that AldA is irreversibly inhibited under H2O2 treatment in vitro due to overoxidation of Cys279 in the absence of BSH. Pre-treatment of AldA with BSH prior to H2O2 exposure resulted in reversible AldA inactivation due to S-bacillithiolation as revealed by activity assays and BSH-specific Western blot analysis. Using molecular docking and molecular dynamic simulation, we further show that BSH occupies two different positions in the AldA active site depending on the AldA activation state. In conclusion, we show here that AldA is an important target for S-bacillithiolation in S. aureus that is up-regulated under NaOCl stress and functions in protection under hypochlorite stress.
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PMID:The aldehyde dehydrogenase AldA contributes to the hypochlorite defense and is redox-controlled by protein S-bacillithiolation in Staphylococcus aureus. 2943 22