Version 1
: Received: 24 April 2023 / Approved: 25 April 2023 / Online: 25 April 2023 (04:06:34 CEST)
How to cite:
Sotoudeheian, M.; Soleimani, M.; Farahmandian, N.; Mirahmadi, S. Molecular Pathways Disturbances during COVID-19 Lead to Cardiomyocyte Necroptosis. Preprints2023, 2023040882. https://doi.org/10.20944/preprints202304.0882.v1
Sotoudeheian, M.; Soleimani, M.; Farahmandian, N.; Mirahmadi, S. Molecular Pathways Disturbances during COVID-19 Lead to Cardiomyocyte Necroptosis. Preprints 2023, 2023040882. https://doi.org/10.20944/preprints202304.0882.v1
Sotoudeheian, M.; Soleimani, M.; Farahmandian, N.; Mirahmadi, S. Molecular Pathways Disturbances during COVID-19 Lead to Cardiomyocyte Necroptosis. Preprints2023, 2023040882. https://doi.org/10.20944/preprints202304.0882.v1
APA Style
Sotoudeheian, M., Soleimani, M., Farahmandian, N., & Mirahmadi, S. (2023). Molecular Pathways Disturbances during COVID-19 Lead to Cardiomyocyte Necroptosis. Preprints. https://doi.org/10.20944/preprints202304.0882.v1
Chicago/Turabian Style
Sotoudeheian, M., Navid Farahmandian and Seyed-Mohamad-Sadegh Mirahmadi. 2023 "Molecular Pathways Disturbances during COVID-19 Lead to Cardiomyocyte Necroptosis" Preprints. https://doi.org/10.20944/preprints202304.0882.v1
Abstract
SARS-CoV-2 was detected in China in December 2019. Myocardial injury is a crucial presentation of COVID-19, based on the association of ACE-2 and SARS-CoV-2. Down-regulating ACE-2 decreases the cardioprotective effects of angiotensin, leading to a higher TNF-α activation. TNF-α causes the inflammatory response in the myocardial damage as an apoptotic inducer. Moreover, as an inducer of necroptosis, TNF-α binds to a part of TNF receptor 1, which involves receptor-interacting protein 1 (RIP1) and causes cell death through RIP1 inhibition and NF-κB stimulation, which are also done through Tpl-2. Calcineurin controls the Tpl-2-driven NFAT stimulation. Bcl-2 or Bcl-XL entirely blocks these pathways. Bcl-2 overexpression reduces FasL expression with a mechanism based on Bcl-2 inhibiting the NFAT. Moreover, the Fas/FasL system activates apoptosis in various cells. Bcl-XL stimulates Fas-related cell death. Additionally, TNF-α, as a part of inflammatory cytokine storms, indirectly interacts with NFAT/Bcl-2 through Tpl-2/NF-κB. Diversely, TNF-α and IL-1ẞ, the basis of inflammatory cytokine storms in COVID-19, can stimulate generating NO. Also, IL-2 is highly up-regulated in COVID-19 patients and stimulates NO generation in patients. TNF-α can provoke the generation of superoxides in neutrophils. A well-determined mechanism is the intracellular production of NO via calcium-calmodulin-dependent NO synthase (NOS). NO enhances NFAT’s calcium-dependent activity. Also, Intra/extracellular calcium exchange activates calcineurin and its related molecule, NFAT. Nitration provokes RIP1 necroptosis cascade, with respiratory complex I. Nitrites converse protection against ischemia-reperfusion injuries in the myocardium. Regulating this intrinsic molecular pathway can prevent the necroptosis of cardiomyocytes.
Keywords
COVID-19; Necroptosis; NFAT; NO; TNF-α; NF-κB
Subject
Medicine and Pharmacology, Cardiac and Cardiovascular Systems
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.