China
Africa
Explore chapters and articles related to this topic
Advancing Phospholipase D Enzymes as Diverse Drug Targets
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Hortênsia Gomes Leala, Kimberly A. Stieglitzb
Autotaxin (ATX) is another important mammalian non-HKDPLD, which has attracted attention as a potential target for drugs. Autotaxin is a glycoprotein that is secreted in cerebrospinal fluid, blood, synovial fluid, and is also abundantly expressed in brain, ovary, placenta, small intestine, lymph nodes, pancreas, testis, kidneys, and lungs (Fotopoulou et al., 2010; Lee et al., 1996; Kawagoe et al., 1995; Palmeri et al., 2004). As a member of the nucleotide pyrophosphatase phosphodiesterase family, autotaxin (EC: 3.1.4.39) perform hydrolysis and transphosphatidylation. This enzyme can convert lysophosphatidylcholine (LPC) to LPA or cyclic LPA (Fig. 4.2B) and hydrolyzes sphingosylphosphorylcholine (SPC) to S1P (Hausmann et al., 2011; Umezu-Goto et al., 2002; Tania et al., 2010). Like NAPE-PLD, ATX uses Ca2+ and Zn2+ divalent ions as cofactors in the active site (Stein et al., 2015). ATX binds to integrin of activated platelets and lymphocytes. Autotaxin and its product LPA were suggested to promote lymphocyte transmigration, enhance lymphocyte motility, and promote lymphocyte entry into secondary lymphoid organs (Kanda et al., 2008; Pamuklar et al., 2009). Also, based on ATX crystal structure analysis, two potential LPA binding sites were found within the ATX structure. This suggest ATX is a lipid carrier protein that delivers LPA to LPA receptors in cell surfaces (Van Meeteren et al., 2007). This ATX-LPA LPA receptor mechanism has been implicated in several human pathologies including inflammation, fibrosis, rheumatism, asthma, neurological disorders, atherosclerosis, and cancer, among others (Dong-Soon Im, 2015; Oikonomou et al., 2012).
Extracellular vesicles released in response to respiratory exposures: implications for chronic disease
Published in Journal of Toxicology and Environmental Health, Part B, 2018
Birke J. Benedikter, Emiel F. M. Wouters, Paul H. M. Savelkoul, Gernot G. U. Rohde, Frank R. M. Stassen
Finally, respiratory exposure-induced EV may contribute to allergic inflammation and development of (occupational) asthma. In ovalbumin-sensitized mice, intratracheally instilled magnetic iron oxide nanoparticles triggered release of EV that promote dendritic cell maturation and T cell activation (Zhu et al. 2012). Brostrom et al. (2015) found that treatment of pulmonary epithelial cells with the occupational respiratory toxicant toluene diisocyanate initiated release of autotaxin via EV, an enzyme that has been implicated in allergic airway inflammation.