Modulating Nitric Oxide: Implications for Cytotoxicity and Cytoprotection

Modulating Nitric Oxide: Implications for Cytotoxicity and Cytoprotection

23 April 2024 | Igor Belenichev, Olena Popazova, Nina Bukhtiyarova, Dmytro Savchenko, Valentyn Oksenchy, Oleksandr Kamysnyi
The review discusses the dual role of nitric oxide (•NO) in both cytoprotection and cytotoxicity, highlighting its complex mechanisms in physiological and pathological conditions. •NO, a small molecule with a simple structure, plays a critical role in various biological processes, including cardiovascular function, the central nervous system, and immune responses. It is produced by nitric oxide synthases (NOS), which include constitutive (cNOS) and inducible (iNOS) forms. cNOS is primarily found in neurons and endothelial cells, while iNOS is mainly expressed in macrophages and is involved in immune responses. The regulation of •NO production is influenced by factors such as calcium levels, calmodulin, and the availability of substrates like L-arginine. •NO can exert both protective and harmful effects. It contributes to cytoprotection by regulating the expression of antiapoptotic proteins and mitochondrial function. However, it can also cause cytotoxicity through the generation of reactive oxygen and nitrogen species, such as peroxynitrite, which can lead to oxidative stress, mitochondrial dysfunction, and apoptosis. The balance between these effects is crucial, as excessive •NO production can lead to cellular damage, while controlled levels may support tissue homeostasis. The review also explores the interaction of •NO with the thiol–disulfide system, which plays a key role in maintaining cellular redox balance. Thiols like glutathione can neutralize •NO and its derivatives, reducing their cytotoxic effects. The dysregulation of •NO production and its interactions with other molecules can contribute to various diseases, including hypertension, neurodegenerative disorders, and inflammatory conditions. The study emphasizes the importance of understanding the mechanisms of •NO modulation to develop therapeutic strategies that can mitigate its harmful effects while preserving its protective functions. The review concludes that the precise regulation of •NO synthesis is essential for maintaining cellular and tissue health, and further research is needed to fully elucidate the complex roles of •NO in both health and disease.The review discusses the dual role of nitric oxide (•NO) in both cytoprotection and cytotoxicity, highlighting its complex mechanisms in physiological and pathological conditions. •NO, a small molecule with a simple structure, plays a critical role in various biological processes, including cardiovascular function, the central nervous system, and immune responses. It is produced by nitric oxide synthases (NOS), which include constitutive (cNOS) and inducible (iNOS) forms. cNOS is primarily found in neurons and endothelial cells, while iNOS is mainly expressed in macrophages and is involved in immune responses. The regulation of •NO production is influenced by factors such as calcium levels, calmodulin, and the availability of substrates like L-arginine. •NO can exert both protective and harmful effects. It contributes to cytoprotection by regulating the expression of antiapoptotic proteins and mitochondrial function. However, it can also cause cytotoxicity through the generation of reactive oxygen and nitrogen species, such as peroxynitrite, which can lead to oxidative stress, mitochondrial dysfunction, and apoptosis. The balance between these effects is crucial, as excessive •NO production can lead to cellular damage, while controlled levels may support tissue homeostasis. The review also explores the interaction of •NO with the thiol–disulfide system, which plays a key role in maintaining cellular redox balance. Thiols like glutathione can neutralize •NO and its derivatives, reducing their cytotoxic effects. The dysregulation of •NO production and its interactions with other molecules can contribute to various diseases, including hypertension, neurodegenerative disorders, and inflammatory conditions. The study emphasizes the importance of understanding the mechanisms of •NO modulation to develop therapeutic strategies that can mitigate its harmful effects while preserving its protective functions. The review concludes that the precise regulation of •NO synthesis is essential for maintaining cellular and tissue health, and further research is needed to fully elucidate the complex roles of •NO in both health and disease.
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Understanding Modulating Nitric Oxide%3A Implications for Cytotoxicity and Cytoprotection