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Chemical compound
Leukotriene C4 (LTC4) is a leukotriene. LTC4 has been extensively studied in the context of allergy and asthma.[1][2] In cells of myeloid origin such as mast cells, its biosynthesis is orchestrated by translocation to the nuclear envelope along with co-localization of cytosolic phospholipase A2 (cPLA2), arachidonate 5-lipoxygenase (5-LO), 5-lipoxygenase-activating protein (FLAP) and LTC4 synthase (LTC4S), which couples glutathione to an LTA4 intermediate. The MRP1 transporter then secretes cytosolic LTC4 and cell surface proteases further metabolize it by sequential cleavage of the γ-glutamyl and glycine residues off its glutathione segment, generating the more stable products LTD4 and LTE4. All three leukotrienes then bind at different affinities to two G-protein coupled receptors: CYSLTR1 and CYSLTR2, triggering pulmonary vasoconstriction and bronchoconstriction.[3]
In cells of non-haematopoietic lineage, endoplasmic reticulum (ER) stress and chemotherapy induce LTC4 biosynthesis by transcriptionally upregulating and activating the enzyme microsomal glutathione-S-transferase 2 (MGST2). ER stress and chemotherapy also trigger nuclear translocation of the two LTC4 receptors. Acting in an intracrine manner, LTC4 then elicits nuclear translocation of NADPH oxidase 4 (NOX4), ROS accumulation and oxidative DNA damage.[4] Besides being a potent lipid mediator in asthma and inflammation, LTC4 was reported to be involved in several other diseases, such as allergic airway diseases, dermatological diseases, cardiovascular diseases, liver injury, atherosclerosis and colon cancer.[5][6][7]
^Jakobsson, Per-Johan; Mancini, Joseph A.; Ford-Hutchinson, Anthony W. (1996-09-06). "Identification and Characterization of a Novel Human Microsomal Glutathione S-Transferase with Leukotriene C4 Synthase Activity and Significant Sequence Identity to 5-Lipoxygenase-activating Protein and Leukotriene C4 Synthase". Journal of Biological Chemistry. 271 (36): 22203–22210. doi:10.1074/jbc.271.36.22203. ISSN 0021-9258. PMID 8703034.
^Di Gennaro, Antonio; Haeggström, Jesper Z. (2012-01-01). "The Leukotrienes: Immune-Modulating Lipid Mediators of Disease". In Alt, Frederick W. (ed.). Chapter Two - The Leukotrienes: Immune-Modulating Lipid Mediators of Disease. Advances in Immunology. Vol. 116. Academic Press. pp. 51–92. doi:10.1016/b978-0-12-394300-2.00002-8. ISBN 9780123943002. PMID 23063073.
^Haeggström, Jesper Z.; Funk, Colin D. (2011-09-22). "Lipoxygenase and Leukotriene Pathways: Biochemistry, Biology, and Roles in Disease". Chemical Reviews. 111 (10): 5866–5898. doi:10.1021/cr200246d. PMID 21936577.
^Dvash, Efrat; Har-Tal, Michal; Barak, Sara; Meir, Ofir; Rubinstein, Menachem (2015-12-11). "Leukotriene C4 is the major trigger of stress-induced oxidative DNA damage". Nature Communications. 6: 10112. Bibcode:2015NatCo...610112D. doi:10.1038/ncomms10112. PMC 4682057. PMID 26656251.
^Ma, Kui-Fen; Yang, Hong-Yu; Chen, Zhe; Qi, Luo-Yang; Zhu, Dan-Yan; Lou, Yi-Jia (2008-05-07). "Enhanced expressions and activations of leukotriene C4 synthesis enzymes in D-galactosamine/lipopolysaccharide-induced rat fulminant hepatic failure model". World Journal of Gastroenterology. 14 (17): 2748–2756. doi:10.3748/wjg.14.2748. ISSN 1007-9327. PMC 2709038. PMID 18461660.
^Rigas, B. (1993). "Altered eicosanoid levels in human colon cancer". J Lab Clin Med. 122 (5): 518–23. PMID 8228569.
^Spanbroek, Rainer; Grabner, Rolf; Lotzer, Katharina; Hildner, Markus; Urbach, Anja; Ruhling, Katharina; Moos, Michael P. W.; Kaiser, Brigitte; Cohnert, Tina U. (2003-02-04). "Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis". Proceedings of the National Academy of Sciences of the United States of America. 100 (3): 1238–1243. Bibcode:2003PNAS..100.1238S. doi:10.1073/pnas.242716099. ISSN 0027-8424. PMC 298757. PMID 12552108.
LeukotrieneC4 (LTC4) is a leukotriene. LTC4 has been extensively studied in the context of allergy and asthma. In cells of myeloid origin such as mast...
Leukotrienes are a family of eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty...
LeukotrieneC4 synthase is an enzyme that in humans is encoded by the LTC4S gene. The protein encoded by this gene, LTC4S (or glutathione S-transferase...
Leukotriene A4 (LTA4) is a leukotriene, and is the precursor for the productions of leukotriene B4 (LTB4) and leukotrieneC4 (LTC4). Following the biosynthesis...
antileukotriene, also known as leukotriene modifier and leukotriene receptor antagonist, is a medication which functions as a leukotriene-related enzyme inhibitor...
Montelukast is in the leukotriene receptor antagonist family of medications. It works by blocking the action of leukotriene D4 in the lungs resulting...
Other leukotrienes that function in a similar manner are leukotrienesC4 and E4. Pharmacological agents that inhibit the function of these leukotrienes are...
Leukotriene-C4 hydrolase (EC 3.4.19.14, gamma-glutamyl leukotrienase) is an enzyme. Gamma-glutamyltransferase 5 (GGT5) is a human gene which encodes an...
act convert 5-HPETE to leukotriene A4 (LTA4). LTA4 is then metabolized either to LTB4 by leukotriene A4 hydrolase or leukotrieneC4 (LTC4) by either LTC4...
(Cysteinyl leukotriene receptor 1) – CYSLTR1;CYSLTR1 is the receptor for LeukotrieneC4 and Leukotriene D4; in binds and responds to leukotrieneC4 more strongly...
Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It has been shown to promote insulin resistance in obese mice. LTB4 is a leukotriene...
elongation and unsaturation. AA is the precursor to some prostaglandins, leukotrienes (LTA, LTB, LTC), thromboxane (TXA) and the N-acylethanolamine (NAE)...
Cysteinyl leukotriene receptor 1, also termed CYSLTR1, is a receptor for cysteinyl leukotrienes (LT) (see cysteinyl leukotrienes). CYSLTR1, by binding...
which in turn converts to various leukotrienes (i.e., leukotriene B4, leukotrieneC4, leukotriene D4, and leukotriene E4) as well as to 5-hydroxyeicosatetraenoic...
class of leukotrienes that contain the amino acid cysteine. These cysteinyl leukotrienes include leukotrieneC4, leukotriene D4, and leukotriene E4, all...
LeukotrieneC4 synthase deficiency is an inborn error of metabolism. Deficiency of LeukotrieneC4 synthase can lead to a reduction in LeukotrieneC4. Mayatepek...
Leukotriene E4 (LTE4) is a cysteinyl leukotriene involved in inflammation. It is known to be produced by several types of white blood cells, including...
mediators from arachidonic acid; some of these mediators include histamine, leukotriene (LTC4 and LTD4 and LTB4), and prostaglandin, which act on proteins (e...
enzyme, its primary substrate (molecule upon which an enzyme acts) is leukotriene B4 (LTB4), an eicosanoid, which is an inflammatory mediator. By hydroxylating...
Zyflo) is an orally active inhibitor of 5-lipoxygenase, and thus inhibits leukotrienes (LTB4, LTC4, LTD4, and LTE4) formation, used for the maintenance treatment...