Hexachlorocyclohexanes affect the arachidonic acid release from phosphatidylinositol but not from other phospholipid classes in tubular cell cultures.
Gamma- and delta-isomers of hexachlorocyclohexane caused marked decreases in the levels of radioactive phospholipids, and increases in the levels of [3H]arachidonate incorporated into free fatty acids in rat renal tubular cells. The increased radioactivity of free fatty acids arises from the decrease of [3H]arachidonate incorporated into phosphatidylinositol, but not into phosphatidylcholine, phosphatidylserine or phosphatidylethanolamine. This fact suggests that phosphatidylinositol can be broken down to the fatty acid from the sn-2 position and lysophospholipid by a phospholipase activity increased by hexachlorocyclohexanes. The observed specific toxicant action could be achieved in two ways: (a) operating upon a specific phospholipase A2 that acts on phosphatidylinositol, but not on other phospholipids as substrates and/or (b) involving substrate-phospholipase A2 interactions. Interestingly, the observed effect of the delta-isomer was more pronounced than that of the gamma-one.
Puente-Fraga
J C
JC
Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá de Henares, Alcala de Henares-Madrid, Spain.
López-Aparicio
P
P
Senar
S
S
Recio
M N
MN
Pérez-Albarsanz
M A
MA
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured / Q000166:cytology / Q000201:enzymology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D007306:Insecticides / Q000494:pharmacology*; D007536:Isomerism; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000201:enzymology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000145:classification / Q000378:metabolism; D051381:Rats; D014316:Tritium / Q000378:metabolism
D005230:Fatty Acids, Nonesterified; D007306:Insecticides; D010716:Phosphatidylinositols; D010743:Phospholipids; D014316:Tritium; D016718:Arachidonic Acid; C086916:delta-hexachlorocyclohexane; D001556:Hexachlorocyclohexane; D010741:Phospholipases A; D054467:Phospholipases A2