Malathion/oxon and lead acetate increase gene expression and protein levels of transient receptor potential canonical channel subunits TRPC1 and TRPC4 in rat endothelial cells of the blood-brain barrier.
This study examined the effects of malathion and lead on transient receptor potential canonical channel TRPC1/TRPC4 channels in rat brain endothelial cells as a mechanism to explain previously noted blood-brain barrier (BBB) permeability induced by these compounds. Lead, malathion, malaoxon and combinations of these were assessed for protein levels and gene expression of TRPC1/C4 at 2, 4, 8, 16, and 24 hours after exposure. Changes in intracellular free calcium dynamics were also assessed. Compounds increased TRPC1 and TRPC4 protein levels as well as gene expression within 4 hours after exposure. Basal levels of intracellular free calcium were also elevated. Increases in gene and protein expression may be associated with an increase in the numbers of TRP channels, and the increases in intracellular calcium may be associated with activation of such channels. Therefore, upregulation and activation of the TRPC1/TRPC4 may be a mechanism by which these neurotoxicants affect BBB permeability.
Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA.
Pergentino
P
Balbuena
Wen
W
Li
Beverly A
BA
Rzigalinski
Marion
M
Ehrich
D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007306:Insecticides / Q000633:toxicity*; D008294:Malathion / Q000031:analogs & derivatives* / Q000633:toxicity; D009942:Organometallic Compounds / Q000633:toxicity*; D051381:Rats; D050052:TRPC Cation Channels / Q000096:biosynthesis* / Q000235:genetics
D007306:Insecticides; D009942:Organometallic Compounds; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel; C096351:transient receptor potential cation channel, subfamily C, member 1; C100082:malaoxon; C008261:lead acetate; D002118:Calcium; D008294:Malathion