TRIMETHYLTIN INDUCES GELATINASE-B AND UROKINASE IN RAT-BRAIN

The neurotoxicant trimethyltin (TMT) increases mRNA levels for cytokin es, tumor necrosis factor-alpha, interleukin-1 alpha, and interleukin- 6. Cytokines induce matrix metalloproteinases (MMPs) and urokinase-typ e plasminogen activator (uPA). MMPs and uPA disrupt extracellular matr ix. Since matrix damage may play a role in the neuropathological chang es seen with TMT toxicity, we determined the effect of TMT on proteoly tic 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-substrat e and casein/plasminogen-substrate zymography. Gelatinase B (92 kDa ty pe IV collagenase) production increased significantly in frontal lobe tissue at 24, 48 and 96 h, and in hippocampus at 48 h compared to sali ne-injected controls. Gelatinase A (72 kDa type IV collagenase) was si gnificantly decreased at 12 and 24 h in frontal lobe compared to contr ols. Urokinase-type PA was significantly increased in hippocampus at 1 2 and 96 h, and in frontal lobe at 96 h compared to controls. Gelatina se B and uPA are up-regulated by TMT in frontal lobe and hippocampus, suggesting that they may contribute to the neuropathology of TMT. (C) 1997 Elsevier Science Ireland Ltd.