Latest Publications

@article{phung_posttranslational_2006,

title = {Posttranslational nitrotyrosination of alpha-tubulin induces cell cycle arrest and inhibits proliferation of vascular smooth muscle cells.},

author = {Anh D. Phung and Karel Soucek and Lukás Kubala and Richart W. Harper and J. Chloë Bulinski and Jason P. Eiserich},

doi = {10.1016/j.ejcb.2006.05.016},

issn = {0171-9335},

year  = {2006},

date = {2006-12-01},

journal = {European journal of cell biology},

volume = {85},

number = {12},

pages = {1241–1252},

abstract = {Hyperproliferation of vascular smooth muscle cells is a hallmark of atherosclerosis and related vascular complications. Microtubules are important for many aspects of mammalian cell responses including growth, migration and signaling. alpha-Tubulin, a component of the microtubule cytoskeleton, is unique amongst cellular proteins in that it undergoes a reversible posttranslational modification whereby the C-terminal tyrosine residue is removed (Glu-tubulin) and re-added (Tyr-tubulin). Whereas the reversible detyrosination/tyrosination cycle of alpha-tubulin has been implicated in regulating various aspects of cell biology, the precise function of this posttranslational modification has remained poorly characterized. Herein, we provide evidence suggesting that alpha-tubulin detyrosination is a required event in the proliferation of vascular smooth muscle cells. Proliferation of rat aortic smooth muscle cells in response to serum was temporally associated with the detyrosination of alpha-tubulin, but not acetylation of alpha-tubulin; Glu-tubulin reached maximal levels between 12 and 18h following cell cycle initiation. Inclusion of 3-nitro-l-tyrosine (NO(2)Tyr) in the culture medium resulted in the selective nitrotyrosination of alpha-tubulin, that was paralleled by decreased elaboration of Glu-tubulin, decreased expression of cyclins A and E, decreased association of the microtubule plus-end binding protein EB1, and inhibited cell proliferation. Nitrotyrosination of alpha-tubulin did not induce necrotic or apoptotic death of rat aortic smooth muscle cells, but instead led to cell cycle arrest at the G(1)/S boundary coincident with decreased DNA synthesis. Collectively, these results suggest that the C-terminus of alpha-tubulin and its detyrosination are functionally important as a molecular switch that regulates cell cycle progression in vascular smooth muscle cells.},

note = {Place: Germany},

keywords = {*Cell Proliferation, Animals, Apoptosis/physiology, Cell Cycle/*physiology, Cells, Cultured, Glutamic Acid/metabolism, Microtubules/physiology, Muscle, Post-Translational/*physiology, Protein Processing, Rats, Smooth, Tubulin/*metabolism, Tyrosine/*analogs & derivatives/metabolism, Vascular/*cytology/physiology},

pubstate = {published},

tppubtype = {article}

}

@article{hoferova_vitro_2004,

title = {In vitro proliferation of fibrosarcoma cells depends on intact functions of lipoxygenases and cytochrome P-450-monooxygenase.},

author = {Zuzana Hoferová and Karel Soucek and Jirina Hofmanová and Michael Hofer and Katerina Chramostová and Peter Fedorocko and Alois Kozubik},

doi = {10.1081/cnv-120030212},

issn = {0735-7907},

year  = {2004},

date = {2004-01-01},

journal = {Cancer investigation},

volume = {22},

number = {2},

pages = {234–247},

abstract = {Proliferation of mouse fibrosarcoma cells G:5:113 was studied in vitro after affecting particular pathways of arachidonic acid metabolism by selected inhibitors. After 48 hours of cultivation with nonspecific lipoxygenase inhibitors, nordihydroguaiaretic acid (NDGA) and esculetin; a specific 12-lipoxygenase inhibitor, baicalein; and inhibitor of five-lipoxygenase activating protein, MK-886, markedly suppressed the number of cells and induced significant changes in cell cycle distribution in a dose-dependent manner. While proadifen, an inhibitor of cytochrome P-450-monooxygenase, applied in low concentrations, increased the cell number, at higher concentrations, it inhibited cell proliferation and significantly changed the cell cycle. Cyclooxygenase inhibitors, ibuprofen, flurbiprofen, and diclofenac suppressed cell numbers only moderately without any changes in the cell cycle. The occurrence of apoptosis was not significant for any of the selected drugs in comparison with untreated control cells. Moreover, not even one of the drugs caused the specific cleavage of poly (ADP-ribose) polymerase to the 89-kDa fragment, however, a decrease in total amount of this protein was observed after treatment with NDGA and esculetin. We conclude that the proliferation ability of fibrosarcoma cells G:5:113 in vitro depends on intact functions of 5-lipoxygenase, 12-lipoxygenase, and cytochrome P-450-monooxygenases, and that the effects of inhibitors do not include regulation of apoptosis.},

note = {Place: England},

keywords = {Animals, Apoptosis, Arachidonic Acid/antagonists & inhibitors/metabolism/*pharmacology, Cell Cycle/*physiology, Cultured, Cytochrome P-450 Enzyme System/*pharmacology, Enzyme Inhibitors/pharmacology, Fibrosarcoma/*pathology/veterinary, Lipoxygenase/*pharmacology, Mice, Tumor Cells},

pubstate = {published},

tppubtype = {article}

}

@article{hoferova_tumor-host_2003,

title = {Tumor-host interactions accompanying the growth of the G:5:113 fibrosarcoma in the mouse: possibilities for a new therapeutic approach?},

author = {Zuzana Hoferová and Antonín Vacek and Michal Hofer and Nadezda O. Macková and Karel Soucek and Alena Egyed and Peter Fedorocko},

doi = {10.1081/cnv-120016419},

issn = {0735-7907},

year  = {2003},

date = {2003-04-01},

journal = {Cancer investigation},

volume = {21},

number = {2},

pages = {227–236},

abstract = {The experiments were aimed at describing in detail some interactions between a solid tumor growing from subcutaneously transplanted G:5:113 fibrosarcoma cells in vivo and its mouse host. The tumor was found to elevate significantly the number of granulocytes in the peripheral blood of the host after having achieved the volume of about 1 cm3 (day 40 after transplantation). Blood plasma from fibrosarcoma-bearing mice stimulated proliferation of progenitor cells for granulocytes and macrophages (GM-CFC) in vitro and suppressed growth of G:5:113 cell population in culture. Interestingly, both effects were observable as early as week 1 when the tumor was still macroscopically invisible and unpalpable. Conditioned medium from cultures of G:5:113 fibrosarcoma cells stimulated proliferation of GM-CFC in vitro. These findings might represent a starting point for studies aimed at designing new therapeutic approaches for the treatment of fibrosarcoma.},

note = {Place: England},

keywords = {Animals, Cell Count, Cell Cycle/*physiology, Cell Division, Cell Survival/*physiology, Conditioned, Culture Media, Cultured, Fibrosarcoma/blood/*pathology, Granulocytes/pathology, Inbred C3H, Leukocyte Count, Mice, Tumor Cells},

pubstate = {published},

tppubtype = {article}

}