Target type: biologicalprocess
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cobalt ion (Co2+) stimulus. [GOC:mah]
Cobalt ions (Co2+) are essential micronutrients required for the activity of various enzymes, particularly those involved in vitamin B12 metabolism. However, at elevated concentrations, cobalt ions can be toxic to organisms, triggering a complex response mechanism.
The response to cobalt ion involves multiple cellular pathways and processes aimed at mitigating the toxic effects. These responses can be broadly categorized into:
1. **Cellular Uptake and Efflux:** Cobalt ions can enter cells through various membrane transporters, including divalent metal transporters (DMTs) and the zinc transporter ZIP8. To maintain homeostasis and prevent accumulation, cells employ efflux mechanisms, such as the ATP-binding cassette (ABC) transporter P-glycoprotein, which actively pumps cobalt ions out of the cell.
2. **Oxidative Stress Response:** Cobalt ions can induce oxidative stress by generating reactive oxygen species (ROS). Cells respond by activating antioxidant defense systems. This involves the upregulation of enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase, which neutralize ROS and prevent damage to cellular components.
3. **DNA Damage Response:** Cobalt ions can bind to DNA and cause DNA damage, including strand breaks and base modifications. Cells activate DNA repair mechanisms, involving enzymes like DNA polymerase and DNA ligase, to repair the damaged DNA and maintain genomic integrity.
4. **Apoptosis and Autophagy:** In response to persistent cobalt ion exposure, cells may undergo apoptosis (programmed cell death) or autophagy (cellular self-eating) to eliminate damaged cells and prevent the spread of toxicity.
5. **Metal Homeostasis Regulation:** The response to cobalt ion also involves the regulation of metal homeostasis. This includes the induction of metallothioneins, small cysteine-rich proteins that bind to heavy metals, including cobalt, and sequester them from critical cellular functions.
The specific mechanisms and pathways involved in the response to cobalt ion can vary depending on the organism, cell type, and the concentration of cobalt ions. Nevertheless, these responses highlight the complex cellular mechanisms that strive to maintain homeostasis and mitigate the toxic effects of cobalt ion exposure.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Caspase-8 | A caspase-8 that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
| Caspase-9 | A caspase-9 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P55211] | Homo sapiens (human) |
| Caspase-3 | A caspase-3 that is encoded in the genome of human. [PRO:JAN, UniProtKB:P42574] | Homo sapiens (human) |
| Cyclic AMP-dependent transcription factor ATF-1 | A cyclic AMP-dependent transcription factor ATF-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P18846] | Homo sapiens (human) |
| Delta-aminolevulinic acid dehydratase | A delta-aminolevulinic acid dehydratase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P13716] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| 3-hydroxyanthranilic acid | 3-hydroxyanthranilate : A hydroxybenzoate that is the conjugate base of 3-hydroxyanthranilic acid. 3-hydroxyanthranilic acid : An aminobenzoic acid that is benzoic acid substituted at C-2 by an amine group and at C-3 by a hydroxy group. It is an intermediate in the metabolism of the amino acid tryptophan. 3-Hydroxyanthranilic Acid: An oxidation product of tryptophan metabolism. It may be a free radical scavenger and a carcinogen. | aminobenzoic acid; monohydroxybenzoic acid | human metabolite; mouse metabolite |
| 4-biphenylylacetic acid | biphenyl-4-ylacetic acid : A monocarboxylic acid in which one of the alpha-hydrogens is substituted by a biphenyl-4-yl group. An active metabolite of fenbufen, it is used as a topical medicine to treat muscle inflammation and arthritis. | biphenyls; monocarboxylic acid | non-steroidal anti-inflammatory drug |
| fenbufen | fenbufen: structure; RN given refers to parent cpd | 4-oxo monocarboxylic acid; biphenyls | non-steroidal anti-inflammatory drug |
| ibuprofen | Midol: combination of cinnamedrine, phenacetin, aspirin & caffeine | monocarboxylic acid | antipyretic; cyclooxygenase 1 inhibitor; cyclooxygenase 2 inhibitor; drug allergen; environmental contaminant; geroprotector; non-narcotic analgesic; non-steroidal anti-inflammatory drug; radical scavenger; xenobiotic |
| indoprofen | indoprofen : A monocarboxylic acid that is propionic acid in which one of the hydrogens at position 2 is substituted by a 4-(1-oxo-1,3-dihydroisoindol-2-yl)phenyl group. Initially used as an anti-inflammatory and analgesic, it was withdrawn from the market due to causing severe gastrointestinal bleeding. It has been subsequently found to increase production of the survival motor neuron protein. Indoprofen: A drug that has analgesic and anti-inflammatory properties. Following reports of adverse reactions including reports of carcinogenicity in animal studies it was withdrawn from the market worldwide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p21) | gamma-lactam; isoindoles; monocarboxylic acid | EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; non-narcotic analgesic; non-steroidal anti-inflammatory drug |
| ketoprofen | ketoprofen : An oxo monocarboxylic acid that consists of propionic acid substituted by a 3-benzoylphenyl group at position 2. Ketoprofen: An IBUPROFEN-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis. | benzophenones; oxo monocarboxylic acid | antipyretic; drug allergen; EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; environmental contaminant; non-steroidal anti-inflammatory drug; xenobiotic |
| ketorolac | 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid : A member of the class of pyrrolizines that is 2,3-dihydro-1H-pyrrolizine which is substituted at positions 1 and 5 by carboxy and benzoyl groups, respectively. ketorolac : A racemate comprising equimolar amounts of (R)-(+)- and (S)-(-)-5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid. While only the (S)-(-) enantiomer is a COX1 and COX2 inhibitor, the (R)-(+) enantiomer exhibits potent analgesic activity. A non-steroidal anti-inflammatory drug, ketorolac is mainly used (generally as the tromethamine salt) for its potent analgesic properties in the short-term management of post-operative pain, and in eye drops to relieve the ocular itching associated with seasonal allergic conjunctivitis. It was withdrawn from the market in many countries in 1993 following association with haemorrhage and renal failure. Ketorolac: A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is an NSAID and is used principally for its analgesic activity. (From Martindale The Extra Pharmacopoeia, 31st ed) | amino acid; aromatic ketone; monocarboxylic acid; pyrrolizines; racemate | analgesic; cyclooxygenase 1 inhibitor; cyclooxygenase 2 inhibitor; non-steroidal anti-inflammatory drug |
| 3,3',4,5'-tetrahydroxystilbene | stilbenoid | ||
| tiaprofenic acid | tiaprofenic acid : An aromatic ketone that is thiophene substituted at C-2 by benzoyl and at C-4 by a 1-carboxyethyl group. tiaprofenic acid: RN given refers to parent cpd; structure | aromatic ketone; monocarboxylic acid; thiophenes | drug allergen; non-steroidal anti-inflammatory drug |
| isoquinoline-1,3,4-trione | isoquinoline-1,3,4-trione: structure in first source | ||
| n-methylisatin | N-methylisatin: structure given in first source | ||
| 1,2-benzisothiazoline-3-one | 1,2-benzisothiazoline-3-one: a preservative in water-based solutions such as paints, cutting fluids, printing inks, cleaning agents, polyvinyl chloride gloves, etc. benzo[d]isothiazol-3-one : An organic heterobicyclic compound based on a fused 1,2-thiazole and benzene bicyclic ring skeleton, with the S atom positioned adjacent to one of the positions of ring fusion. | organic heterobicyclic compound; organonitrogen heterocyclic compound | disinfectant; drug allergen; environmental contaminant; platelet aggregation inhibitor; sensitiser; xenobiotic |
| etoposide | beta-D-glucoside; furonaphthodioxole; organic heterotetracyclic compound | antineoplastic agent; DNA synthesis inhibitor | |
| 2,2'-((3,3'-dimethoxy(1,1'-biphenyl)-4,4'-diyl)diimino)bis-benzoic acid | 2,2'-((3,3'-dimethoxy(1,1'-biphenyl)-4,4'-diyl)diimino)bis-benzoic acid: structure given in first source | ||
| stictic acid | stictic acid: antioxidant from lichen, Usnea articulata; structure in first source | aromatic ether | |
| 1-benzylpiperazine | 1-benzylpiperazine : A tertiary amino compound that is piperazine substituted by a benzyl group at position 1. It is a serotonergic agonist used as a recreational drug. 1-benzylpiperazine: possesses psychomotor stimulant activity similar to dextroamphetamine; RN given refers to parent cpd; structure | N-alkylpiperazine | environmental contaminant; psychotropic drug; serotonergic agonist; xenobiotic |
| pralnacasan | pralnacasan: NSAID, ICE inhibitor & metastasis inhibitor; RN & structure in first source | ||
| naproxen | naproxen : A methoxynaphthalene that is 2-methoxynaphthalene substituted by a carboxy ethyl group at position 6. Naproxen is a non-steroidal anti-inflammatory drug commonly used for the reduction of pain, fever, inflammation and stiffness caused by conditions such as osteoarthritis, kidney stones, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, menstrual cramps, tendinitis, bursitis, and for the treatment of primary dysmenorrhea. It works by inhibiting both the COX-1 and COX-2 enzymes. Naproxen: An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout. | methoxynaphthalene; monocarboxylic acid | antipyretic; cyclooxygenase 1 inhibitor; cyclooxygenase 2 inhibitor; drug allergen; environmental contaminant; gout suppressant; non-narcotic analgesic; non-steroidal anti-inflammatory drug; xenobiotic |
| 2-phenyl-1,2-benzisothiazol-3-(2h)-one | 2-phenyl-1,2-benzisothiazol-3-(2H)-one: structure given in first source; sulfur analog of ebselen | ||
| (R)-Roemerine | isoquinoline alkaloid | ||
| 1,3(2h,4h)-isoquinolinedione | 1,3(2H,4H)-isoquinolinedione: structure in first source | ||
| 5-benzimidazolecarboxylic acid | 5-benzimidazolecarboxylic acid: structure in first source | ||
| acetyl-aspartyl-glutamyl-valyl-aspartal | Ac-Asp-Glu-Val-Asp-H : A tetrapeptide consisting of two L-aspartic acid residues, an L-glutamyl residue and an L-valine residue with an acetyl group at the N-terminal and with the C-terminal carboxy group reduced to an aldehyde. It is an inhibitor of caspase-3/7. acetyl-aspartyl-glutamyl-valyl-aspartal: a capase inhibitor | tetrapeptide | protease inhibitor |
| 1,6-dimethyl-3-(2-pyridinyl)pyrimido[5,4-e][1,2,4]triazine-5,7-dione | pyrimidotriazine | ||
| 1,6-dimethyl-3-propylpyrimido[5,4-e][1,2,4]triazine-5,7-dione | pyrimidotriazine | ||
| 5-Nitroisatin | indoles | anticoronaviral agent | |
| n-acetyltyrosyl-valyl-alanyl-aspartyl aldehyde | |||
| benzyloxycarbonyl-phe-ala-fluormethylketone | cathepsin B inhibitor : A cysteine protease inhibitor which inhibits cathepsin B (EC 3.4.22.1). | ||
| benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone | |||
| sp 100030 | N-(3,5-bis(trifluoromethyl)phenyl)-2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxamide: transcription factor inhibitor specific to T-cells | ||
| acetic acid 2-[4-methyl-8-(4-morpholinylsulfonyl)-1,3-dioxo-2-pyrrolo[3,4-c]quinolinyl]ethyl ester | pyrroloquinoline | ||
| pf 03491390 | |||
| grassystatin a | grassystatin A: isolated from a cyanobacterium, identified as Lyngbya cf.; structure in first source | ||
| MK-8353 | MK-8353 : A member of the class of indazoles that is 1H-indazole substituted by a 6-(propan-2-yloxy)pyridin-3-yl group at position 3 and by a {[(3S)-3-(methylsulfanyl)-1-(2-{4-[4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl]-3,6-dihydropyridin-1(2H)-yl}-2-oxoethyl)pyrrolidin-3-yl]carbonyl}amino group at position 5. It is a potent and selective inhibitor of ERK1 and ERK2 in vitro (IC50 values of 23.0 nM and 8.8 nM, respectively). The drug is being developed by Merck Sharp & Dohme and is currently in clinical development for the treatment of advanced/metastatic solid tumors. MK-8353: ERK inhibitor used in oncology | aromatic ether; dihydropyridine; indazoles; methyl sulfide; N-alkylpyrrolidine; pyridines; pyrrolidinecarboxamide; secondary carboxamide; tertiary carboxamide; triazoles | antineoplastic agent; apoptosis inducer; EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor |
| 2-carboxyarabinitol 1-phosphate |