REGULATION OF ZINC PROTEINS AND CELLULAR ZINC HOMEOSTASIS

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Toxic manifestation of coplanar PCB is thought to be mediated by aromatic hydrocarbon (Ah)-receptor. However, the suppression of protein expression by coplanar PCBs is scarcely clarified. We report here the suppression of cytosolic proteins by a coplanar PCB-treatment and propose new aspects of the toxicity. Male Wistar rats were treated with PenCB (single 25 mg/kg, i. p.). Free- and pair-fed control groups were treated with vehicle. At the day 5, the liver cytosol was prepared. The cytosolic proteins were compared among three groups by SDS-PAGE and two-dimensional RAGE (2D-PAGE). Expression level of cytosolic 40-kDa and 27-kDa proteins in rat liver were markedly suppressed by PenCB-treatment. The 40-kDa proteins were identified as aldolase B (Ald B) and alcohol dehydrogenase (ADH) class I by amino acid sequencing of the internal peptides. The 27-kDa protein was also identified as carbonic anhydrase III (CA II). The liver cytosolic Ald and ADH activities were significantly reduced to about 50% and 60% of both control groups by PenCB-treatment. Immunoblotting after sD-PAGE demonstrated that Ald B was markedly suppressed by PenCB-treatment, while change in Ald A was slight. The reduction of ADH by PenCB-treatment was also verified by immunoblotting. The significant suppression of CA III by PenCB-treatment in rat liver was demonstrated by immunoblotting using CA III-selective antibody. Ald plays an important role in glycolytic and gluconeogenetic pathways. In addition, ADH catalyzes biotransformation of triose phosphate to glycerol-3-phosphate. Sippression of Ald B and ADH may be a key biochemical lesion for disordered intermediary metabolism occurring by PenCB-treatment and should be taken into an account as a cause of the wasting syndrom which is a severe toxic effect of toxic coplanar PCBs. CA III possesses tyrosine phosphatase activity, therefore, its suppression could account for the effects on signal transduction by toxic coplanar PCBs.