scholarly journals Mitochondrial targets for pharmacological regulation of cell adaptation to hypoxia

2014 ◽  
Vol 12 (2) ◽  
pp. 28-35 ◽  
Author(s):  
Vasiliy Egorovich Novikov ◽  
Olga Sergeevna Levchenkova
Keyword(s):  
Nitric Oxide ◽  
Adaptation To Hypoxia ◽  
Oxygen Species ◽  
Promising Direction ◽  
Cell Adaptation ◽  
Target Action ◽  
Mitochondrial Nitric Oxide Synthase ◽  
Pharmacological Regulation ◽  
Oxide Synthase

The review is devoted to the role of a number of mitochondrial factors in the regulation of cell adaptation to hypoxia and ischemia. The mechanisms of cell adaptation involving factors such as the mitochondrial ATP-dependent potassium channel, mitochondrial megapora, mitochondrial nitric oxide synthase, reactive oxygen species are discussed in the paper. The possibility of pharmacological regulation of cell adaptation with help of target action on mitochondrial components is proposed. This approach is a promising direction for drug discovery for correction of diseases with hypoxia and ischemia in their pathogenesis.

Mitochondrial nitric oxide synthase and its role in the mechanisms of cell adaptation to hypoxia

2016 ◽  
Vol 14 (2) ◽  
pp. 38-46 ◽  
Author(s):  
Vasiliy E Novikov ◽  
Olga S Levchenkova ◽  
Elena V Pozhilova
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Specific Protein ◽  
New Drugs ◽  
Adaptation To Hypoxia ◽  
Cell Adaptation ◽  
Protein Factor ◽  
Action Analysis ◽  
Mitochondrial Nitric Oxide Synthase ◽  
Oxide Synthase

Mitochondrial nitric oxide synthase (mtNOS) actively participates in mechanisms of regulation of cell adaptation to extreme factors. It is closely interacted with other mitochondrial regulatory factors and is involved in adaptation reactions of cells to hypoxia, ischemia and other pathogenic action. Analysis of the role of mtNOS in cell functioning in hypoxia condition and its influence on apoptosis is presented in the article. Complex mechanism of cell adaptation with participation of mitochondrial nitric oxide (NO) is considered. Mitochondrial NO is a modulator of cell respiration, synthesis of ATP, activity of mitochondrial ATP-sensitive potassium channels, mitochondrial megapore and the specific protein factor to hypoxia adaptation. The possibility of pharmacological regulation of mtNOS activity is discussed. This approach seems to be promising for searching of new drugs for the pharmacotherapy of diseases with hypoxia and ischemia in their pathogenesis. There is possible to regulate cell homeostasis, for example, resistance to hypoxia by modulating the activity of mtNOS and synthesis of mitochondrial NO.

scholarly journals The Protective Role of Bacillus Anthracis Exosporium in Macrophage-Mediated Killing by Nitric Oxide

2007 ◽  
Author(s):  
John Weaver ◽  
Tae Jin Kang ◽  
Kimberly Raines ◽  
Guan-Liang Cao ◽  
Stephen Hibbs ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bacillus Anthracis ◽  
Protective Role ◽  
Oxygen Species ◽  
Activated Macrophages ◽  
Positive Bacterium ◽  
Bacterium Bacillus ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The ability of the endospore-forming, gram-positive bacterium Bacillus anthracis to survive exposure to antibacterial killing mechanisms by activated macrophages is key to its germination and survival. These antibacterial killing mechanisms include, but are not limited to the generation of free radicals such as nitric oxide (•NO) and superoxide (O2•−) from the upregulation of inducible nitric oxide synthase (NOS 2) along with products derived from them, e.g., peroxynitrite (ONOO−), as part of microbicidal activity. However questions still remain as to how these species are involved in microbial killing, specifically with respect to B. anthracis. In a previous study, we demonstrated that exposure of primary murine macrophages to sonicated B. anthracis endospores up-regulated NOS 2 and demonstrated a •NO-dependent bactericidal response, but unanswered in that study was which of the NOS 2-derived reactive oxygen species was responsible for the observed bactericidal response. Since NOS 2 also generates O2•−, experiments were designed to determine whether NOS 2 formed ONOO− from the reaction of •NO with O2•− and if so, was ONOO− microbicidal toward B. anthracis.

scholarly journals Myeloid-Derived Suppressor Cells in Trypanosoma cruzi Infection

2021 ◽  
Vol 11 ◽  
Author(s):  
Manuel Fresno ◽  
Núria Gironès
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Trypanosoma Cruzi ◽  
Reactive Oxygen ◽  
Suppressor Cells ◽  
Oxygen Species ◽  
Arginase 1 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Myeloid-derived suppressor cells (MDSCs) are immature heterogeneous myeloid cells that expand in pathologic conditions as cancer, trauma, and infection. Although characterization of MDSCs is continuously revisited, the best feature is their suppressor activity. There are many markers for MDSC identification, it is distinctive that they express inducible nitric oxide synthase (iNOS) and arginase 1, which can mediate immune suppression. MDSCs can have a medullary origin as a result of emergency myelopoiesis, but also can have an extramedullary origin. Early studies on Trypanosoma cruzi infection showed severe immunosuppression, and several mechanisms involving parasite antigens and host cell mediators were described as inhibition of IL-2 and IL-2R. Another mechanism of immunosuppression involving tumor necrosis factor/interferon γ-dependent nitric oxide production by inducible nitric oxide synthase was also described. Moreover, other studies showed that nitric oxide was produced by CD11b+ Gr-1+ MDSCs in the spleen, and later iNOS and arginase 1 expressed in CD11b+Ly6C+Ly6Glo monocytic MDSC were found in spleen and heart of T. cruzi infected mice that suppressed T cell proliferation. Uncontrolled expansion of monocytic MDSCs leads to L-arginine depletion which hinders nitric oxide production leading to death. Supplement of L-arginine partially reverts L-arginine depletion and survival, suggesting that L-arginine could be administered along with anti-parasitical drugs. On the other hand, pharmacological inhibition of MDSCs leads to death in mice, suggesting that some expansion of MDSCs is needed for an efficient immune response. The role of signaling molecules mediating immune suppression as reactive oxygen species, reactive nitrogen species, as well as prostaglandin E2, characteristics of MDSCs, in T. cruzi infection is not fully understood. We review and discuss the role of these reactive species mediators produced by MDSCs. Finally, we discuss the latest results that link the SLAMF1 immune receptor with reactive oxygen species. Interaction of the parasite with the SLAMF1 modulates parasite virulence through myeloid cell infectivity and reactive oxygen species production. We discuss the possible strategies for targeting MDSCs and SLAMF1 receptor in acute Trypanosoma cruzi infection in mice, to evaluate a possible translational application in human acute infections.

Sign in / Sign up

Export Citation Format

Share Document