Čeština
EnglishEvaluation of novel microtubules interfering agents myoseverin, tubulyzine and E2GG in primary cultures of rat hepatocytes
Dvořák, Z.; Modrianský, M.; Vrba, J.; Ulrichová, J.; Kryštof, Vladimír; Stýskala, Jakub; Pávek, P.
GENERAL PHYSIOLOGY AND BIOPHYSICS 26 [3]: 173-180, 2007
Klíčová slova: microtubule; tubulin polymerization; cytochrome P450
Abstrakt: We investigated the effects of novel microtubules interfering agents (MIAs) in primary cultures of rat hepatocytes. Cells were treated for 24 h with a known compound colchicine and newly synthesized derivatives myoseverin, tubulyzine, and E2GG. We examined the effects of MIAs on microtubules network integrity and on the polymerization capability of isolated tubulin. All tested MIAs inhibited microtubules assembly with the following IC50 values: tubulyzine (4.4 +/- 0.9 mu mol/1), myoseverin (7.0 +/- 0.8 mu mol/1), E2GG (16 +/- 2 mu mol/1), colchicine (2.0 +/- 0.4 mu mol/1). The potency of MIAs to perturb microtubular network integrity (monitored by immune-histochemistry) increased in the order tubulyzine < myoseverin < E2GG < colchicine. We described recently deleterious effects of MIAs on the expression of drug metabolizing enzymes, including CYPIAI Here we observed inhibitory effects of novel MIAs on dioxin-inducible expression of CYP1A1 mRNA in rat hepatocytes. We conclude that novel MIAs exert analogical biological response as classical MIAs such as colchicine or nocodazole. This further supports the hypothesis that tubulin is the primordial target of MIAs within the cell and that perturbation of microtubules dynamics and/or integrity triggers the biological effects described here.
DOI:
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GENERAL PHYSIOLOGY AND BIOPHYSICS 26 [3]: 173-180, 2007
Klíčová slova: microtubule; tubulin polymerization; cytochrome P450
Abstrakt: We investigated the effects of novel microtubules interfering agents (MIAs) in primary cultures of rat hepatocytes. Cells were treated for 24 h with a known compound colchicine and newly synthesized derivatives myoseverin, tubulyzine, and E2GG. We examined the effects of MIAs on microtubules network integrity and on the polymerization capability of isolated tubulin. All tested MIAs inhibited microtubules assembly with the following IC50 values: tubulyzine (4.4 +/- 0.9 mu mol/1), myoseverin (7.0 +/- 0.8 mu mol/1), E2GG (16 +/- 2 mu mol/1), colchicine (2.0 +/- 0.4 mu mol/1). The potency of MIAs to perturb microtubular network integrity (monitored by immune-histochemistry) increased in the order tubulyzine < myoseverin < E2GG < colchicine. We described recently deleterious effects of MIAs on the expression of drug metabolizing enzymes, including CYPIAI Here we observed inhibitory effects of novel MIAs on dioxin-inducible expression of CYP1A1 mRNA in rat hepatocytes. We conclude that novel MIAs exert analogical biological response as classical MIAs such as colchicine or nocodazole. This further supports the hypothesis that tubulin is the primordial target of MIAs within the cell and that perturbation of microtubules dynamics and/or integrity triggers the biological effects described here.
DOI: