Desmin Reorganization by Stimuli Inducing Oxidative Stress and Electrophiles: Role of Its Single Cysteine Residue
The type III intermediate filament proteins vimentin and GFAP are modulated by oxidants and electrophiles, mainly through perturbation of their single cysteine residues. Desmin, the type III intermediate filament protein specific to muscle cells, is critical for muscle homeostasis, playing a key rol...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/9/1703 |
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| author | Diego Moneo-Corcuera Álvaro Viedma-Poyatos Konstantinos Stamatakis Dolores Pérez-Sala |
| author_facet | Diego Moneo-Corcuera Álvaro Viedma-Poyatos Konstantinos Stamatakis Dolores Pérez-Sala |
| author_sort | Diego Moneo-Corcuera |
| collection | DOAJ |
| description | The type III intermediate filament proteins vimentin and GFAP are modulated by oxidants and electrophiles, mainly through perturbation of their single cysteine residues. Desmin, the type III intermediate filament protein specific to muscle cells, is critical for muscle homeostasis, playing a key role in sarcomere organization and mitochondrial function. Here, we have studied the impact of oxidants and cysteine-reactive agents on desmin behavior. Our results show that several reactive species and drugs induce covalent modifications of desmin in vitro, of which its single cysteine residue, C333, is an important target. Moreover, stimuli eliciting oxidative stress or lipoxidation, including H<sub>2</sub>O<sub>2</sub>, 15-deoxy-prostaglandin J<sub>2</sub>, and CoCl<sub>2</sub>-elicited chemical hypoxia, provoke desmin disorganization in H9c2 rat cardiomyoblasts transfected with wild-type desmin, which is partially attenuated in cells expressing a C333S mutant. Notably, in cells lacking other cytoplasmic intermediate filaments, network formation by desmin C333S appears less efficient than that of desmin wt, especially when these proteins are expressed as fluorescent fusion constructs. Nevertheless, in these cells, the desmin C333S organization is also protected from disruption by oxidants. Taken together, our results indicate that desmin is a target for oxidative and electrophilic stress, which elicit desmin remodeling conditioned by the presence of its single cysteine residue. |
| first_indexed | 2024-03-10T23:06:47Z |
| format | Article |
| id | doaj.art-ba6575fc96fc4e398e68be5f09773425 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T23:06:47Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-ba6575fc96fc4e398e68be5f097734252023-11-19T09:19:14ZengMDPI AGAntioxidants2076-39212023-08-01129170310.3390/antiox12091703Desmin Reorganization by Stimuli Inducing Oxidative Stress and Electrophiles: Role of Its Single Cysteine ResidueDiego Moneo-Corcuera0Álvaro Viedma-Poyatos1Konstantinos Stamatakis2Dolores Pérez-Sala3Department of Structural and Chemical Biology, Centro de Investigaciones Biológicas Margarita Salas (CSIC), 28040 Madrid, SpainDepartment of Structural and Chemical Biology, Centro de Investigaciones Biológicas Margarita Salas (CSIC), 28040 Madrid, SpainDepartamento de Biología Molecular, Universidad Autónoma de Madrid (UAM), 28049 Madrid, SpainDepartment of Structural and Chemical Biology, Centro de Investigaciones Biológicas Margarita Salas (CSIC), 28040 Madrid, SpainThe type III intermediate filament proteins vimentin and GFAP are modulated by oxidants and electrophiles, mainly through perturbation of their single cysteine residues. Desmin, the type III intermediate filament protein specific to muscle cells, is critical for muscle homeostasis, playing a key role in sarcomere organization and mitochondrial function. Here, we have studied the impact of oxidants and cysteine-reactive agents on desmin behavior. Our results show that several reactive species and drugs induce covalent modifications of desmin in vitro, of which its single cysteine residue, C333, is an important target. Moreover, stimuli eliciting oxidative stress or lipoxidation, including H<sub>2</sub>O<sub>2</sub>, 15-deoxy-prostaglandin J<sub>2</sub>, and CoCl<sub>2</sub>-elicited chemical hypoxia, provoke desmin disorganization in H9c2 rat cardiomyoblasts transfected with wild-type desmin, which is partially attenuated in cells expressing a C333S mutant. Notably, in cells lacking other cytoplasmic intermediate filaments, network formation by desmin C333S appears less efficient than that of desmin wt, especially when these proteins are expressed as fluorescent fusion constructs. Nevertheless, in these cells, the desmin C333S organization is also protected from disruption by oxidants. Taken together, our results indicate that desmin is a target for oxidative and electrophilic stress, which elicit desmin remodeling conditioned by the presence of its single cysteine residue.https://www.mdpi.com/2076-3921/12/9/1703cysteine modificationintermediate filamentscytoskeletal organizationoxidative stressprotein lipoxidation |
| spellingShingle | Diego Moneo-Corcuera Álvaro Viedma-Poyatos Konstantinos Stamatakis Dolores Pérez-Sala Desmin Reorganization by Stimuli Inducing Oxidative Stress and Electrophiles: Role of Its Single Cysteine Residue Antioxidants cysteine modification intermediate filaments cytoskeletal organization oxidative stress protein lipoxidation |
| title | Desmin Reorganization by Stimuli Inducing Oxidative Stress and Electrophiles: Role of Its Single Cysteine Residue |
| title_full | Desmin Reorganization by Stimuli Inducing Oxidative Stress and Electrophiles: Role of Its Single Cysteine Residue |
| title_fullStr | Desmin Reorganization by Stimuli Inducing Oxidative Stress and Electrophiles: Role of Its Single Cysteine Residue |
| title_full_unstemmed | Desmin Reorganization by Stimuli Inducing Oxidative Stress and Electrophiles: Role of Its Single Cysteine Residue |
| title_short | Desmin Reorganization by Stimuli Inducing Oxidative Stress and Electrophiles: Role of Its Single Cysteine Residue |
| title_sort | desmin reorganization by stimuli inducing oxidative stress and electrophiles role of its single cysteine residue |
| topic | cysteine modification intermediate filaments cytoskeletal organization oxidative stress protein lipoxidation |
| url | https://www.mdpi.com/2076-3921/12/9/1703 |
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