Are acantholysis and transglutaminase inhibition related phenomena?

Dermatology : International Journal for Clinical and Investigative Dermatology
C EspositoR Porta

Abstract

The loss of intercellular cohesion among keratinocytes (acantholysis) may be considered the histologic marker of pemphigus. Many drugs, especially thiol drugs, proved to be able to provoke in vitro acantholysis by biochemical mechanisms interfering with the disulfide and thiol group balance. As to nonthiol drugs, the pathomechanism of acantholysis is still unexplained. To explain the molecular mechanism of enalapril-induced acantholysis a potential link between transglutaminase (TGase) activity and the effects of this drug was investigated. TGase activity in extracts from human breast skin cultured in the presence of thiopronine, captopril and enalapril were evaluated in vitro. The acantholytic potential of cystamine, a known TGase inhibitor, was also investigated. Enalapril, the most powerful acantholytic drug in vitro, was found to inhibit both the purified enzyme and the TGase activity in the extracts from cultured human breast skin explants. Kinetic studies showed that enalapril inhibition was competitive with respect to the amino acceptor substrate and uncompetitive with respect to the amino donor substrate. Moreover, an acantholytic effect of cystamine on explants of normal human skin was shown. These results suggest that...Continue Reading

Citations

Dec 6, 2000·The Australasian Journal of Dermatology·C S OngS Lee
Jan 17, 2007·The British Journal of Dermatology·C A HarrisonS MacNeil
Oct 1, 2010·The Journal of Law, Medicine & Ethics : a Journal of the American Society of Law, Medicine & Ethics·Sally Wang
Sep 18, 2010·The British Journal of Dermatology·T ZeeliA Ravid
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