Lysophosphatidic acids
Lysophosphatidic acids (LPA) are phosphoglycerolipids with a free hydroxyl group and thus belong to the phospholipids . They have one acyl group less than most phosphoglycerolipids and belong to the lysophosphatides . As secondary messenger substances, LPA are involved in the prevention of apoptosis , in cell division and cell migration .
properties
Lysophosphatidic acids are formed from phosphoglycerolipids by enzymatic hydrolysis of an acyl group and then by hydrolysis of the end group on the phosphate from a lysophosphatide. As a result, the lysophosphatidic acid has a free hydroxyl group. In addition, an acyl group and a phosphate group are bound to the other two theoretically possible hydroxyl groups on the glycerol backbone . The acyl group can consist of various fatty acids .
Outside of cells, LPA is mainly formed from the most abundant lipid in blood plasma , lysophosphatidylcholine , by the enzyme autotaxin .
LPA are mitogens through the activation of the G protein-coupled receptors LPAR1 (EDG2), LPAR2 (EDG4), LPAR3 (EDG7), LPAR4 (P2RY9, GPR23), LPAR5 (GPR92) and LPAR6 (P2RY5, GPR87). As a result, the GTPase Rho and thereby the Rho kinase is activated. About a subsequent inhibition of myosin light chain kinase are stress fibers formed and promoted cell migration.
In cancer , LPAs promote some resistance to chemotherapy and radiation therapy, as well as angiogenesis and metastasis .
Individual evidence
- ↑ a b c d M. G. Benesch, YM Ko, TP McMullen, DN Brindley: Autotaxin in the crosshairs: taking aim at cancer and other inflammatory conditions. In: FEBS letters. Volume 588, number 16, August 2014, pp. 2712-2727, doi : 10.1016 / j.febslet.2014.02.009 , PMID 24560789 .