Evaluation of novel microtubules interfering agents myoseverin, tubulyzine and E2GG in primary cultures of rat hepatocytes

0305969 - ÚEB 2008 RIV SK eng J - Journal Article
Dvořák, Z. - Modrianský, M. - Vrba, J. - Ulrichová, J. - Kryštof, Vladimír - Stýskala, Jakub - Pávek, P.
Evaluation of novel microtubules interfering agents myoseverin, tubulyzine and E2GG in primary cultures of rat hepatocytes.
[Evaluation of novel microtubules interfering agents myoseverin, tubulyzine and E2GG in primary cultures of rat hepatocytes.]
General Physiology and Biophysics. Roč. 26, č. 3 (2007), s. 173-180. ISSN 0231-5882. E-ISSN 1338-4325
Grant - others:Univerzita Palackého v Olomouci / Přírodovědecká fakulta(CZ) GP204/03/D231
Institutional research plan: CEZ:AV0Z50380511
Source of funding: V - Other public resources
Keywords : microtubule * tubulin polymerization * cytochrome P450
Subject RIV: CE - Biochemistry
Impact factor: 1.286, year: 2007
http://www.gpb.sav.sk/2007-3.htm

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.

Evaluation of novel microtubules interfering agents myoseverin, tubulyzine and E2GG in primary cultures of rat hepatocytes.
Permanent Link: http://hdl.handle.net/11104/0159090