Target type: biologicalprocess
Any process that stops, prevents, or reduces the frequency, rate or extent of the controlled release of an icosanoid from a cell. [GOC:mah]
Negative regulation of icosanoid secretion is a crucial cellular process that governs the controlled release of icosanoids, signaling molecules derived from arachidonic acid. These molecules, including prostaglandins, thromboxanes, leukotrienes, and lipoxins, play pivotal roles in inflammation, immunity, and various physiological functions. To maintain cellular homeostasis and prevent excessive inflammation, cells employ intricate mechanisms to tightly regulate icosanoid secretion. This process involves a cascade of events, starting with the activation of phospholipase A2 (PLA2), which liberates arachidonic acid from membrane phospholipids. Arachidonic acid is then metabolized by different enzyme pathways, namely cyclooxygenases (COX) and lipoxygenases (LOX), leading to the production of various icosanoids. Several factors contribute to the negative regulation of icosanoid secretion:
1. **Inhibition of PLA2 activity:** Specific inhibitors like lipocortins and annexins can block the activity of PLA2, preventing the initial release of arachidonic acid.
2. **Downregulation of COX and LOX enzymes:** The expression and activity of COX and LOX enzymes can be reduced by various mechanisms, such as transcriptional repression, protein degradation, or competitive inhibition by specific inhibitors.
3. **Increased synthesis of anti-inflammatory mediators:** Cells can produce anti-inflammatory molecules like lipoxins and resolvins, which antagonize the pro-inflammatory effects of icosanoids, ultimately reducing their overall production.
4. **Activation of signaling pathways that suppress icosanoid synthesis:** Certain signaling pathways, such as the cAMP pathway, can inhibit the activity of COX and LOX enzymes, thereby decreasing icosanoid secretion.
5. **Regulation of icosanoid receptors:** Cells express various receptors for icosanoids, and these receptors can be modulated to fine-tune the cellular response to icosanoids. For example, downregulation of pro-inflammatory icosanoid receptors can reduce the overall inflammatory response.
6. **Induction of anti-inflammatory transcription factors:** Nuclear factors like NF-κB can be activated, leading to the transcription of genes encoding anti-inflammatory mediators, further contributing to the suppression of icosanoid secretion.
These complex and tightly regulated processes ensure that icosanoid secretion is appropriately controlled, preventing excessive inflammation and maintaining cellular homeostasis.'
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Protein | Definition | Taxonomy |
---|---|---|
Cytochrome P450 4F2 | A cytochrome P450 4F2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P78329] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
17-octadecynoic acid | octadec-17-ynoic acid : An acetylenic fatty acid that is octadecanoi acid (stearic acid) which has been doubly dehydrogenated at positions 17 and 18 to give the corresponding alkynoic acid. | acetylenic fatty acid; long-chain fatty acid; monounsaturated fatty acid; terminal acetylenic compound | EC 1.14.14.94 (leukotriene-B4 20-monooxygenase) inhibitor; EC 1.14.15.3 (alkane 1-monooxygenase) inhibitor; P450 inhibitor |
ketoconazole | 1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine : A dioxolane that is 1,3-dioxolane which is substituted at positions 2, 2, and 4 by imidazol-1-ylmethyl, 2,4-dichlorophenyl, and [para-(4-acetylpiperazin-1-yl)phenoxy]methyl groups, respectively. | dichlorobenzene; dioxolane; ether; imidazoles; N-acylpiperazine; N-arylpiperazine | |
tranylcypromine | (1R,2S)-tranylcypromine : A 2-phenylcyclopropan-1-amine that is the (1R,2S)-enantiomer of tranylcypromine. tranylcypromine : A racemate comprising equal amounts of (1R,2S)- and (1S,2R)-2-phenylcyclopropan-1-amine. An irreversible monoamine oxidase inhibitor that is used as an antidepressant (INN tranylcypromine). Tranylcypromine: A propylamine formed from the cyclization of the side chain of amphetamine. This monoamine oxidase inhibitor is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders. (From AMA Drug Evaluations Annual, 1994, p311) | 2-phenylcyclopropan-1-amine | |
proadifen hydrochloride | |||
pirlindole | pirlindole: RN given refers to parent cpd; synonym pyrazidol refers to mono-HCl; structure in Negwer, 5th ed, #2812 | carbazoles | |
kaf156 | ganaplacide: antimalarial |