Molecular mechanisms of homocysteine toxicity.
Hyperhomocysteinemia is a risk factor for a number of cardiovascular and neurodegenerative processes as well as a complicating factor in normal pregnancy. Toxic effects of homocysteine and the product of its spontaneous oxidation, homocysteic acid, are based on their ability to activate NMDA receptors, increasing intracellular levels of ionized calcium and reactive oxygen species. Even a short-term exposure of cells to homocysteic acid at concentrations characteristic of hyperhomocysteinemia induces their apoptotic transformation. The discovery of NMDA receptors both in neuronal tissue and in several other tissues and organs (including immunocompetent cells) makes them a target for toxic action of homocysteine. The neuropeptide carnosine was found to protect the organism from homocysteine toxicity. Treatment of pregnant rats with carnosine under conditions of alimentary hyperhomocysteinemia increases viability and functional activity of their progeny.
Boldyrev
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Biological Faculty, Lomonosov Moscow State University, Moscow, 119992, Russia. alexander.boldyrev@gmail.com
D000818:Animals; D017209:Apoptosis; D001773:Blood Cells / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000209:etiology*; D002336:Carnosine / Q000494:pharmacology / Q000502:physiology; D005260:Female; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D008297:Male; D019636:Neurodegenerative Diseases / Q000209:etiology*; D009474:Neurons / Q000187:drug effects; D011247:Pregnancy; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism; D012307:Risk Factors
D016194:Receptors, N-Methyl-D-Aspartate; D006710:Homocysteine; C007956:homocysteic acid; D002336:Carnosine