211
Bis Avenue Kennedy - BP 1140
03103 Montluçon cedex - France
Tel. (33) (0) 4 70 03 88 55
Fax. (33) (0) 4 70 03 82 60
Hot line
(33) (0) 04 70 03 73 06
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MDA is a physiological compound produced by peroxidative decomposition of unsaturated lipids as a by-product of arachidonic metabolism. Under normal conditions, MDA is quickly oxidized to acetate or malonate and then to CO2 via TCA cycle. Excessive production of MDA, as a result of tissue injury and DNA-damage, could combine with free amino groups of proteins resulting into MDA-modified protein adducts. Modifications of proteins by MDA could conceivably alter biological properties of proteins. Moreover, MDA-modified protein may serve as an antigen and invoke production of autoantibodies and subsequent destruction of MDA-modified proteins. An uncontrolled diabetes mellitus is known to be associated with high free radical activity. Injections if streptozotocin has been shown to induce MDA-modified proteins in the plasma. MDA-modified LDL shows altered behavior and is entrapped in arterial walls. Autoantibodies to MDA-LDL have been detected in human and rabbits sera. Moreover, alcohol fed rats and alcoholics have autoantibodies to acetaldehyde. Further progress in this field is hampered by the availability of anti-MDA antibodies. Among the aldehyde which originate from the peroxidation of cellular membrane lipids, 4-hydroxy-2-nonenal (HNE) is the major aldehyde generated by free radical attack on w-6 polyunsaturated fatty acids. HNE is largely responsible for pathogenesis during oxidative stress. HNE is highly reactive towards free sulfydryl groups of proteins producing thioether adducts that further undergo cyclization to form hemiacetals. HNE also reacts with histidine and lysine residues of proteins to form stable Michael addition-type adducts. HNE induces heat shock protein, inhibits cellular proliferation and highly toxic to cells. It exhibits genotoxic and mutagenic effects as well. Elevated levels of HNE modified nigral neurons were also observed in Parkinson disease. ADI has produced antibodies to MDA and HNE to further investigate the role of MDA/HNE-modification in cellular physiology. In addition, ELISA kits have been developed to assess the presence of auto-antibodies to MDA/HNE in mouse. |
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211
Bis Avenue Kennedy - BP 1140 Tel. (33) (0) 4 70 03 88 55 Fax. (33) (0) 4 70 03 82 60 |
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Hot line (33) (0) 04 70 03 73 06 |
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