Effects of neurotoxic chemicals on brain creatine kinase activities and its genetic expression

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We have found that typical neurotoxic chemicals, i.e., acrylamide, ethylene oxide and methyl bromide, all inhibit creatine kinase (CK) activities in vitro (rat brain homogenate) and in vivo (rat and mouse). In this study, we have examined whether acrylamide impairs genetic expression of CK by utilizing RT-PCR and Western blotting to measure CK mRNA and CK protein level, respectively. As a result, we found no changes in mRNA of cytosolic CK (B subunit) and mitochondrial CK (ubiquitous form) or in protein level of cytosolic CK. Thus, apparent inhibition of CK activities by acrylamide in the brain is not caused by suppression of genetic expression of the enzyme.CK catalyzes the reaction ; ATP + creatine ←→ ADP + phosphocreatine. In view of the importance of maintaining constant energy (ATP) supply to the brain, inhibition of CK activities may be related to the neurotoxicity. Moreover, since the concept of "phosphocreatine shuttle" where CK plays a key role in both directions has been established, importance of the inhibition of CK activities by representative neurotoxic chemicals seem to be larger than before.