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Experimental methyl mercury encephalopathy: mechanisms of mercurial perturbation of rat brain protein synthesis

Thesis/Dissertation ·
OSTI ID:5487844
Attempts were made to characterize the mechanism(s) of action of methyl mercury chloride (MeHg) on rat brain protein synthesis. Single i.p. injection of MeHg to young rats resulted in a dose-dependent stimulation followed by inhibition of amino acid incorporation in postmitochondrial supernatant (PMS) after 18-24 hours. Isolated ribosomes revealed a similar biphasic mercurial perturbation of amino acid incorporation when supplemented with homologous pH 5 enzymes, but these effects were reversed by substituting cytosolic pH 5 enzymes derived from control animals. In agreement with the in vivo results, a biphasic mercurial effect was observed following in vitro addition of MeHg to the PMS and to the ribosomal amino acid incorporating systems. The mercurial induced stimulation of translation appeared to be associated with an increase in the formation of 40S pre-initiation complex and 80S initiation units. The similarities in the lesions produced in vivo and in vitro suggested direct interaction of the organic heavy metal with protein synthetic targets in the brain. A model was proposed to explain the variable action of MeHg in the brain suggesting a possible existence of an endogenous inhibitor of protein synthesis that was sensitive to MeHg.
Research Organization:
California Univ., Los Angeles (USA)
OSTI ID:
5487844
Country of Publication:
United States
Language:
English