Trimethyltin induces gelatinase B and urokinase in rat brain.
The neurotoxicant trimethyltin (TMT) increases mRNA levels for cytokines, tumor necrosis factor-alpha, interleukin-1alpha, and interleukin-6. Cytokines induce matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA). MMPs and uPA disrupt extracellular matrix. Since matrix damage may play a role in the neuropathological changes seen with TMT toxicity, we determined the effect of TMT on proteolytic enzyme production. Adult rats were injected with 8.0 mg TMT/kg. At different times after TMT injection, tissue samples from frontal lobe and hippocampus were assayed for MMPs and uPA, using gelatin-substrate and casein/plasminogen-substrate zymography. Gelatinase B (92 kDa type IV collagenase) production increased significantly in frontal lobe tissue at 24, 48 and 96 h, and in hippocampus at 48 h compared to saline-injected controls. Gelatinase A (72 kDa type IV collagenase) was significantly decreased at 12 and 24 h in frontal lobe compared to controls. Urokinase-type PA was significantly increased in hippocampus at 12 and 96 h, and in frontal lobe at 96 h compared to controls. Gelatinase B and uPA are up-regulated by TMT in frontal lobe and hippocampus, suggesting that they may contribute to the neuropathology of TMT.
Dencoff
J E
JE
Department of Neurology, University of New Mexico School of Medicine, Albuquerque 87131, USA.
Rosenberg
G A
GA
Harry
G J
GJ
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D017364:Collagenases / Q000096:biosynthesis*; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects / Q000201:enzymology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D008297:Male; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000096:biosynthesis; D010960:Plasminogen Activators / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014298:Trimethyltin Compounds / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis*
D014298:Trimethyltin Compounds; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D017364:Collagenases; D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9