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Figure 1 | BMC Pharmacology and Toxicology

Figure 1

From: Role of astrocytes in manganese mediated neurotoxicity

Figure 1

A proposed model describing the mechanisms of Mn-mediated disruption of glutamine/glutamate-GABA cycle. Mn exposure leads to the deregulation of Gln uptake by dysfunction of SNAT3 and ASCT2 activity, while incubation with BIS II (bisindolylmaleimide, general PKC inhibitor) reverses this effect (1); Mn exposure leads to the deregulation of Glu uptake by dysfunction of GLT1 and GLAST activity, while incubation with BIS II, Gö6976 (PKCα inhibitor) , ROT (rottlerin, PKCδ inhibitor) and Z-VAD-FMK (Z-Ala-Glu(OMe)-Val-Asp(OMe)-fluoromethyl ketone caspase inhibitor) reverses this effect (2); Mn exposure leads to the activation of PKCδ and PKCα (3); additionally, Mn mediates activation of PKCδ by caspase-3-dependent proteolytic cleavage (4); proteolytically activated PKCδ translocates to the nucleus and mediates DNA fragmentation (5); Mn-mediated disruption of SNAT3, ASCT2 and GLT1 expression involves PKCδ signalling (6,7); GLAST expression is down regulated by Mn via PKCα signalling (8).

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