3H-PDBu binding after administration of methylmercury to mice.

Abstract

Methylmercury has been recognized as an extremely hazardous environmental and industrial pollutant. Evidence would suggest that the primary site of action of methylmercury toxicity is limited to the neural tissues. The mechanism underlying its toxicity is apparently related to its extreme high affinity to the sulfhydryl groups of proteins. Recently, much attention has been focused on protein kinase C, which is known to be the target of tumor promoting phorbol esters including phorbol 12,13-dibutylate (PDBu), as a key enzyme in signal transduction for various biologically active substances. Protein kinase C is ubiquitous in tissues and organs although the highest concentration is found in neural tissues. Moreover, sequence studies revealed that protein kinase C is different from other protein kinases because it is rich in cysteine. Thus, it is reasonable to assume that the mode of action of methylmercury is by impairment of protein kinase C activity, thereby bringing about neuronal dysfunctions. In the present study, the authors evaluated the effects of methylmercury on protein kinase C in vivo by determining {sup 3}H-PDBu binding in several tissues from methylmercury-administered mice.