Signaling Mechanisms and Disrupted Cytoskeleton in the Diphenyl Ditelluride Neurotoxicity
Figure 4
Schematic representation of the proposed mechanism of action of (PhTe)2 on the IF-associated phosphorylating system of cerebral cortex neural cells of young rats in vitro. (PhTe)2 acts in NMDA and VDCC channels, increasing intracellular Ca+2 levels. The second messenger directly inhibits AC and PKA activities, decreases the phosphorylation level of DARPP-32 (Thr-34), and releases PP1 activity. Taken together, these actions change the phosphorylation status of IF proteins in vitro. NMDA, N-methyl-D-aspartate receptor; VDCC, voltage-dependent calcium channel; PKA, cAMP-dependent protein kinase; DARPP-32, dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa; PP1, phosphoprotein phosphatase 1; PP2b, calcineurin; AC, adenylate cyclase. Orange-red circles represent Ca+2.
