Target type: biologicalprocess
Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a nitrosative stress stimulus. Nitrosative stress is a state often resulting from exposure to high levels of nitric oxide (NO) or the highly reactive oxidant peroxynitrite, which is produced following interaction of NO with superoxide anions. [GOC:mah]
Nitrosative stress is a cellular condition characterized by an imbalance in the production and detoxification of reactive nitrogen species (RNS), primarily nitric oxide (NO) and its derivatives. RNS can cause a range of damaging effects, including protein modification, DNA damage, and lipid peroxidation. Cells have evolved complex mechanisms to respond to nitrosative stress, aiming to mitigate these harmful effects and maintain cellular homeostasis.
The cellular response to nitrosative stress involves a multi-layered network of signaling pathways and enzymatic activities.
1. **Detection and Signaling:** The initial step involves the sensing of RNS by specific cellular sensors. These sensors include redox-sensitive proteins like thioredoxins, peroxiredoxins, and glutathione S-transferases, which undergo conformational changes upon encountering RNS. This triggers downstream signaling cascades, often involving the activation of transcription factors like Nrf2 and NF-κB.
2. **Antioxidant Defense:** Cells deploy a battery of antioxidant enzymes to neutralize RNS. Superoxide dismutase (SOD) converts superoxide radicals (O2-) into hydrogen peroxide (H2O2), which is further reduced to water by catalase or glutathione peroxidases. Glutathione reductase, in conjunction with NADPH, keeps glutathione in its reduced state, enhancing its antioxidant capacity.
3. **Repair Mechanisms:** Nitrosative stress can induce DNA damage, protein misfolding, and lipid peroxidation. Cells have repair mechanisms in place to deal with these damages. DNA repair pathways, such as base excision repair (BER) and nucleotide excision repair (NER), remove damaged bases and repair DNA breaks. Molecular chaperones like Hsp70 assist in protein refolding, while enzymes like glutathione S-transferases detoxify lipid peroxidation products.
4. **Regulation of Gene Expression:** Transcription factors like Nrf2 and NF-κB play crucial roles in regulating gene expression in response to nitrosative stress. Upon activation, Nrf2 promotes the expression of genes involved in antioxidant defense, detoxification, and cellular repair. NF-κB, on the other hand, regulates genes involved in inflammation, apoptosis, and immune responses.
5. **Apoptosis and Autophagy:** In cases of severe or prolonged nitrosative stress, cells may initiate apoptosis (programmed cell death) to eliminate damaged cells and prevent further damage to the organism. Autophagy, a process of cellular self-eating, can also be triggered to remove damaged organelles and proteins, thereby promoting cellular survival.
The cellular response to nitrosative stress is a complex and dynamic process that involves intricate interplay between signaling pathways, enzymatic activities, and gene expression. The balance between RNS production and detoxification is crucial for maintaining cellular homeostasis. Dysregulation of these processes can contribute to the pathogenesis of various diseases, including cancer, neurodegenerative diseases, and cardiovascular diseases.'
```"
Protein | Definition | Taxonomy |
---|---|---|
Serine-protein kinase ATM | A serine-protein kinase ATM that is encoded in the genome of human. [PRO:CNA] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
pd 173074 | aromatic amine; biaryl; dimethoxybenzene; pyridopyrimidine; tertiary amino compound; ureas | antineoplastic agent; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor; fibroblast growth factor receptor antagonist | |
caffeine | purine alkaloid; trimethylxanthine | adenosine A2A receptor antagonist; adenosine receptor antagonist; adjuvant; central nervous system stimulant; diuretic; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; environmental contaminant; food additive; fungal metabolite; geroprotector; human blood serum metabolite; mouse metabolite; mutagen; plant metabolite; psychotropic drug; ryanodine receptor agonist; xenobiotic | |
2-(4-morpholinyl)-8-phenyl-4h-1-benzopyran-4-one | 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one: specific inhibitor of phosphatidylinositol 3-kinase; structure in first source | chromones; morpholines; organochlorine compound | autophagy inhibitor; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor; geroprotector |
schizandrin b | schizandrin B: a phytogenic antineoplastic agent with anti-inflammatory activity; isolated from Schisandra plant | ||
thiourea | thiourea : The simplest member of the thiourea class, consisting of urea with the oxygen atom substituted by sulfur. Thiourea: A photographic fixative used also in the manufacture of resins. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance may reasonably be anticipated to be a carcinogen (Merck Index, 9th ed). Many of its derivatives are ANTITHYROID AGENTS and/or FREE RADICAL SCAVENGERS. | one-carbon compound; thioureas; ureas | antioxidant; chromophore |
ku 55933 | 2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one: specific inhibitor of the ataxia-telangiectasia mutated kinase ATM; structure in first source | ||
cgk 733 | diarylmethane | ||
nu 7026 | 2-(morpholin-4-yl)benzo(h)chromen-4-one: a radiosensitizing agent that inhibits DNA-dependent protein kinase; structure in first source | organic heterotricyclic compound; organooxygen compound | |
nu 7441 | 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one: structure in first source | dibenzothiophenes | |
ku-0060648 | dibenzothiophenes | ||
dactolisib | dactolisib : An imidazoquinoline that is 3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinoline substituted at position 1 by a 4-(1-cyanoisopropyl)phenyl group and at position 8 by a quinolin-3-yl group. A dual PI3K/mTOR inhibitor used in cancer treatment. dactolisib: antineoplastic agent that inhibits both phosphatidylinositol 3-kinase and mTOR | imidazoquinoline; nitrile; quinolines; ring assembly; ureas | antineoplastic agent; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor; mTOR inhibitor |
ku 60019 | |||
cp 466722 | quinazolines | ||
(3R)-4-[2-(1H-indol-4-yl)-6-(1-methylsulfonylcyclopropyl)-4-pyrimidinyl]-3-methylmorpholine | indoles | ||
ve 821 | 3-amino-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide: an antineoplastic agent; structure in first source | aromatic amide | |
torin 2 | torin 2 : A member of the class of pyridoquinolines that is benzo[h][1,6]naphthyridin-2-one carrying additional 3-(trifluoromethyl)phenyl and 6-aminopyridin-3-yl substituents at positions 1 and 9 respectively. It is a potent inhibitor of mTOR and exhibits anti-cancer properties. | aminopyridine; organofluorine compound; primary amino compound; pyridoquinoline | antineoplastic agent; mTOR inhibitor |
byl719 | proline derivative | ||
cc-115 | 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino(2,3-b)pyrazin-2(1H)-one: an mTOR kinase inhibitor; structure in first source | ||
vx-970 | berzosertib: an ATR kinase inhibitor | sulfonamide | |
etp-46464 | ETP-46464: inhibits ATM and Rad3-related kinase; structure in first source |