The Role of Signaling Pathways of Inflammation and Oxidative Stress in Development of Senescence and Aging Phenotypes in Cardiovascular Disease
The ASK1-signalosome→p38 MAPK and SAPK/JNK signaling networks promote senescence (in vitro) and aging (in vivo, animal models and human cohorts) in response to oxidative stress and inflammation. These networks contribute to the promotion of age-associated cardiovascular diseases of oxidati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/11/1383 |
| _version_ | 1797721849176522752 |
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| author | John Papaconstantinou |
| author_facet | John Papaconstantinou |
| author_sort | John Papaconstantinou |
| collection | DOAJ |
| description | The ASK1-signalosome→p38 MAPK and SAPK/JNK signaling networks promote senescence (in vitro) and aging (in vivo, animal models and human cohorts) in response to oxidative stress and inflammation. These networks contribute to the promotion of age-associated cardiovascular diseases of oxidative stress and inflammation. Furthermore, their inhibition delays the onset of these cardiovascular diseases as well as senescence and aging. In this review we focus on whether the (a) ASK1-signalosome, a major center of distribution of reactive oxygen species (ROS)-mediated stress signals, plays a role in the promotion of cardiovascular diseases of oxidative stress and inflammation; (b) The ASK1-signalosome links ROS signals generated by dysfunctional mitochondrial electron transport chain complexes to the p38 MAPK stress response pathway; (c) the pathway contributes to the sensitivity and vulnerability of aged tissues to diseases of oxidative stress; and (d) the importance of inhibitors of these pathways to the development of cardioprotection and pharmaceutical interventions. We propose that the ASK1-signalosome regulates the progression of cardiovascular diseases. The resultant attenuation of the physiological characteristics of cardiomyopathies and aging by inhibition of the ASK1-signalosome network lends support to this conclusion. Importantly the ROS-mediated activation of the ASK1-signalosome p38 MAPK pathway suggests it is a major center of dissemination of the ROS signals that promote senescence, aging and cardiovascular diseases. Pharmacological intervention is, therefore, feasible through the continued identification of potent, non-toxic small molecule inhibitors of either ASK1 or p38 MAPK activity. This is a fruitful future approach to the attenuation of physiological aspects of mammalian cardiomyopathies and aging. |
| first_indexed | 2024-03-12T09:40:04Z |
| format | Article |
| id | doaj.art-6570fcdbe94641879a221e816fa67346 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T09:40:04Z |
| publishDate | 2019-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-6570fcdbe94641879a221e816fa673462023-09-02T13:20:51ZengMDPI AGCells2073-44092019-11-01811138310.3390/cells8111383cells8111383The Role of Signaling Pathways of Inflammation and Oxidative Stress in Development of Senescence and Aging Phenotypes in Cardiovascular DiseaseJohn Papaconstantinou05.138B Medical Research Building, 301 University Boulevard, Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX 77555-0643, USAThe ASK1-signalosome→p38 MAPK and SAPK/JNK signaling networks promote senescence (in vitro) and aging (in vivo, animal models and human cohorts) in response to oxidative stress and inflammation. These networks contribute to the promotion of age-associated cardiovascular diseases of oxidative stress and inflammation. Furthermore, their inhibition delays the onset of these cardiovascular diseases as well as senescence and aging. In this review we focus on whether the (a) ASK1-signalosome, a major center of distribution of reactive oxygen species (ROS)-mediated stress signals, plays a role in the promotion of cardiovascular diseases of oxidative stress and inflammation; (b) The ASK1-signalosome links ROS signals generated by dysfunctional mitochondrial electron transport chain complexes to the p38 MAPK stress response pathway; (c) the pathway contributes to the sensitivity and vulnerability of aged tissues to diseases of oxidative stress; and (d) the importance of inhibitors of these pathways to the development of cardioprotection and pharmaceutical interventions. We propose that the ASK1-signalosome regulates the progression of cardiovascular diseases. The resultant attenuation of the physiological characteristics of cardiomyopathies and aging by inhibition of the ASK1-signalosome network lends support to this conclusion. Importantly the ROS-mediated activation of the ASK1-signalosome p38 MAPK pathway suggests it is a major center of dissemination of the ROS signals that promote senescence, aging and cardiovascular diseases. Pharmacological intervention is, therefore, feasible through the continued identification of potent, non-toxic small molecule inhibitors of either ASK1 or p38 MAPK activity. This is a fruitful future approach to the attenuation of physiological aspects of mammalian cardiomyopathies and aging.https://www.mdpi.com/2073-4409/8/11/1383cardiomyopathiessenescenceagingoxidative stressinflammationmitochondrial dysfunctionask1-signalosomep38 mapk |
| spellingShingle | John Papaconstantinou The Role of Signaling Pathways of Inflammation and Oxidative Stress in Development of Senescence and Aging Phenotypes in Cardiovascular Disease Cells cardiomyopathies senescence aging oxidative stress inflammation mitochondrial dysfunction ask1-signalosome p38 mapk |
| title | The Role of Signaling Pathways of Inflammation and Oxidative Stress in Development of Senescence and Aging Phenotypes in Cardiovascular Disease |
| title_full | The Role of Signaling Pathways of Inflammation and Oxidative Stress in Development of Senescence and Aging Phenotypes in Cardiovascular Disease |
| title_fullStr | The Role of Signaling Pathways of Inflammation and Oxidative Stress in Development of Senescence and Aging Phenotypes in Cardiovascular Disease |
| title_full_unstemmed | The Role of Signaling Pathways of Inflammation and Oxidative Stress in Development of Senescence and Aging Phenotypes in Cardiovascular Disease |
| title_short | The Role of Signaling Pathways of Inflammation and Oxidative Stress in Development of Senescence and Aging Phenotypes in Cardiovascular Disease |
| title_sort | role of signaling pathways of inflammation and oxidative stress in development of senescence and aging phenotypes in cardiovascular disease |
| topic | cardiomyopathies senescence aging oxidative stress inflammation mitochondrial dysfunction ask1-signalosome p38 mapk |
| url | https://www.mdpi.com/2073-4409/8/11/1383 |
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