Leukotriene C4

Leukotriene C4

Identifiers
CAS Number	72025-60-6 Y
ChEBI	CHEBI:16978 Y
KEGG	C02166 Y
MeSH	Leukotriene+C4
Properties
Chemical formula	C30H47N3O9S
Molar mass	625.775 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

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]

Eicosanoid synthesis. (Leukotrienes at right.)

References