title: Cytotoxicity of RNases is increased by cationization and counteracted by K(Ca) channels.
abstract: K(Ca) channels are involved in control of cell proliferation and differentiation. Here we have revealed their role in overcoming the RNase-induced cytotoxicity. Toxic effects of Streptomyces aureofaciens RNases Sa, Sa2, Sa3, and of RNase Sa charge reversal mutants on the human embryonic kidney cell lines differing only by the presence of K(Ca) channels were characterized. In contrast to other RNases, a basic variant of RNase Sa and RNase Sa3 exhibit significant cytotoxic activity of the same order of magnitude as onconase. Our data indicate the absence of a correlation between catalytic activity and stability of RNases and cytotoxicity. On the other hand, cationization enhances toxic effect of an RNase indicating the major role of a positive charge. Essentially lower sensitivity to cytotoxic microbial RNases of cells expressing K(Ca) channels was found. These results suggest that cells without the K(Ca) channel activity cannot counteract toxic effect of RNases.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, 119991 Moscow, Russia.
authors.forename: Olga N
authors.initials: ON
authors.lastname: Ilinskaya
authors.forename: Andreas
authors.initials: A
authors.lastname: Koschinski
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Mitkevich
authors.forename: Holger
authors.initials: H
authors.lastname: Repp
authors.forename: Florian
authors.initials: F
authors.lastname: Dreyer
authors.forename: C Nick
authors.initials: CN
authors.lastname: Pace
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Makarov
mesh_terms: D015220:Calcium Channels / Q000737:chemistry*; D002384:Catalysis; D002412:Cations; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D007668:Kidney; D020033:Protein Isoforms; D012260:Ribonucleases / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D013304:Streptomyces aureofaciens / Q000201:enzymology*; D013696:Temperature; D014162:Transfection
chemical_list: D015220:Calcium Channels; D002412:Cations; D020033:Protein Isoforms; D012260:Ribonucleases