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Lipids in Health and Disease

, 5:1

First Online: 23 January 2006Received: 15 November 2005Accepted: 23 January 2006

Abstract

Homocysteine is an independent risk factor for cardiovascular diseases. It is also known to be associated with a variety of complex disorders. While there are a large number of independent studies implicating homocysteine in isolated pathways, the mechanism of homocysteine induced adverse effects are not clear. Homocysteine-induced modulation of gene expression through alteration of methylation status or by hitherto unknown mechanisms is predicted to lead to several pathological conditions either directly or indirectly. In the present manuscript, using literature mining approach, we have identified the genes that are modulated directly or indirectly by an elevated level of homocysteine. These genes were then placed in appropriate pathways in an attempt to understand the molecular basis of homocysteine induced complex disorders and to provide a resource for selection of genes for polymorphism screening and analysis of mutations as well as epigenetic modifications in relation to hyperhomocysteinemia. We have identified 135 genes in 1137 abstracts that either modulate the levels of homocysteine or are modulated by elevated levels of homocysteine. Mapping the genes to their respective pathways revealed that an elevated level of homocysteine leads to the atherosclerosis either by directly affecting lipid metabolism and transport or via oxidative stress and-or Endoplasmic Reticulum ER stress. Elevated levels of homocysteine also decreases the bioavailability of nitric oxide and modulates the levels of other metabolites including S-adenosyl methionine and S-adenosyl homocysteine which may result in cardiovascular or neurological disorders. The ER stress emerges as the common pathway that relates to apoptosis, atherosclerosis and neurological disorders and is modulated by levels of homocysteine. The comprehensive network collated has lead to the identification of genes that are modulated by homocysteine indicating that homocysteine exerts its effect not only through modulating the substrate levels for various catalytic processes but also through regulation of expression of genes involved in complex diseases.

List of abbreviationsB2Vitamin B2

B12Vitamin B12

5f-THF5-formyltetrahydrofolate

5-CH3THF5-methyltetrahydrofolate

dUMPUridine -5-prime monophosphate

dUTMPTymidine -5-prime monophosphate

DMGDimethylglycine

DMGDHDimethylglycine Dehydrogenase

MMetal catalysed

ERKPPhophorylation of Extracellular signal regulated kinase

eIF-2αEukaryote initiation factor 2 α

CHOPC-EBP-homologous protein

PERKPKR-like endoplasmic reticulum eIF2alpha kinase

CEBPBCCAAT-enhancer -binding protein alpha

EGR1Early growth response 1

CCND1Cyclin D1

IL6RInterleukin 6 receptor

LEPLeptin

LEPRLeptin receptor

PTX3Pentraxin 3

STAT3Signal Transducer And Activator Of Transcription 3

TNFRSF1BTumor Necrosis Factor Receptor Member 1A

PLA2Phospholipase A2

LOXLipoxygenase

COXCycloxygenase

PSPhosphatidyl Serine

PARPPoly-ADP-ribosome polymerase

Electronic supplementary materialThe online version of this article doi:10.1186-1476-511X-5-1 contains supplementary material, which is available to authorized users.

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Autor: Priyanka Sharma - RD Senthilkumar - Vani Brahmachari - Elayanambi Sundaramoorthy - Anubha Mahajan - Amitabh Sharma - Shantan

Fuente: https://link.springer.com/







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