Functional inhibition of redox regulated heme proteins: A novel mechanism towards oxidative stress induced by homocysteine
Homocysteine (Hcy) is a sulfur containing non-protein toxic amino acid synthesized from methionine. Elevated level of Hcy is associated with cardiovascular complications and neurodegeneration. Hcy is believed to induce organ damage and apoptosis via oxidative stress. The pro-oxidant nature of Hcy is...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-10-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231721002391 |
| _version_ | 1819105398826729472 |
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| author | Gurumayum Suraj Sharma Reshmee Bhattacharya Laishram Rajendrakumar Singh |
| author_facet | Gurumayum Suraj Sharma Reshmee Bhattacharya Laishram Rajendrakumar Singh |
| author_sort | Gurumayum Suraj Sharma |
| collection | DOAJ |
| description | Homocysteine (Hcy) is a sulfur containing non-protein toxic amino acid synthesized from methionine. Elevated level of Hcy is associated with cardiovascular complications and neurodegeneration. Hcy is believed to induce organ damage and apoptosis via oxidative stress. The pro-oxidant nature of Hcy is considered to originate from the metal-induced oxidation of thiol group-containing molecules forming disulfides (Hcy-Hcy, Hcy-cysteine, Hcy-glutathione, etc) or with free cysteine residues of proteins (a process called protein S-homocysteinylation). Formation of such disulfides indeed results in the generation of reactive oxygen species (ROS) which eventually leads to loss of cellular integrity. In the present manuscript, we performed systematic investigation of the effect of Hcy on iron containing proteins. We discover a novel mechanism of Hcy toxicity wherein Hcy oxidation is linked with the functional loss of the protein with iron as cofactors. Our results indicate that redox regulated heme proteins might be primarily involved in the Hcy toxicity and associated oxidative stress. |
| first_indexed | 2024-12-22T02:21:37Z |
| format | Article |
| id | doaj.art-0ae865e6343546daa801d95468f6c32e |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-22T02:21:37Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-0ae865e6343546daa801d95468f6c32e2022-12-21T18:42:06ZengElsevierRedox Biology2213-23172021-10-0146102080Functional inhibition of redox regulated heme proteins: A novel mechanism towards oxidative stress induced by homocysteineGurumayum Suraj Sharma0Reshmee Bhattacharya1Laishram Rajendrakumar Singh2Department of Botany, Bhaskaracharya College of Applied Sciences, University of Delhi, Delhi, 110075, IndiaDr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110007, IndiaDr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110007, India; Corresponding author.Homocysteine (Hcy) is a sulfur containing non-protein toxic amino acid synthesized from methionine. Elevated level of Hcy is associated with cardiovascular complications and neurodegeneration. Hcy is believed to induce organ damage and apoptosis via oxidative stress. The pro-oxidant nature of Hcy is considered to originate from the metal-induced oxidation of thiol group-containing molecules forming disulfides (Hcy-Hcy, Hcy-cysteine, Hcy-glutathione, etc) or with free cysteine residues of proteins (a process called protein S-homocysteinylation). Formation of such disulfides indeed results in the generation of reactive oxygen species (ROS) which eventually leads to loss of cellular integrity. In the present manuscript, we performed systematic investigation of the effect of Hcy on iron containing proteins. We discover a novel mechanism of Hcy toxicity wherein Hcy oxidation is linked with the functional loss of the protein with iron as cofactors. Our results indicate that redox regulated heme proteins might be primarily involved in the Hcy toxicity and associated oxidative stress.http://www.sciencedirect.com/science/article/pii/S2213231721002391HomocystinuriaHeme proteinsOxidative stress |
| spellingShingle | Gurumayum Suraj Sharma Reshmee Bhattacharya Laishram Rajendrakumar Singh Functional inhibition of redox regulated heme proteins: A novel mechanism towards oxidative stress induced by homocysteine Redox Biology Homocystinuria Heme proteins Oxidative stress |
| title | Functional inhibition of redox regulated heme proteins: A novel mechanism towards oxidative stress induced by homocysteine |
| title_full | Functional inhibition of redox regulated heme proteins: A novel mechanism towards oxidative stress induced by homocysteine |
| title_fullStr | Functional inhibition of redox regulated heme proteins: A novel mechanism towards oxidative stress induced by homocysteine |
| title_full_unstemmed | Functional inhibition of redox regulated heme proteins: A novel mechanism towards oxidative stress induced by homocysteine |
| title_short | Functional inhibition of redox regulated heme proteins: A novel mechanism towards oxidative stress induced by homocysteine |
| title_sort | functional inhibition of redox regulated heme proteins a novel mechanism towards oxidative stress induced by homocysteine |
| topic | Homocystinuria Heme proteins Oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S2213231721002391 |
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