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Cell Transition (cell + transition)
Selected AbstractsCell-cycle deregulation in BALB/c 3T3 cells transformed by 1,2-dibromoethane and folpet pesticidesENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 5 2003Maria Alessandra Santucci Abstract The cell-transforming potential of 1,2-dibromoethane and folpet, two widely used agricultural pesticides that are potential sources of environmental pollution, has been previously ascribed to their promoting activity. In this study, we investigated whether BALB/c 3T3 transformation by these chemicals was associated with the deregulation of signals involved in cell-cycle progression and in cell-cycle checkpoint induction. We found that two BALB/c 3T3 cell clones transformed by in vitro medium-term (8-week) exposure to the carcinogens had a constitutive acceleration of cell transition from G1 to S phase and an abrogation of the radiation-induced G1/S checkpoint. These events involved multiple signals; in particular, the inhibitors of cyclin/cyclin-dependent kinase complexes p21 and p27 were significantly down-modulated and the positive regulators of cell-cycle progression cyclin D3 and E were up-modulated. As anticipated for cells where the G1/S checkpoint was abrogated, the transformed cells exhibited a significant reinforcement of the radiation-induced G2/M checkpoint, the only checkpoint remaining to protect genomic integrity. However, cyclin A1 and B1 coexpression and cyclin A1 overexpression were found despite the G2 arrest in irradiated cells and these signals likely attenuate the G2/M checkpoint. These alterations to normal cell cycling may promote the emergence of both numerical and structural chromosomal abnormalities and their tolerance. Such a condition could play a key role in neoplastic transformation and be crucial in tumor progression. Furthermore, cyclin A1 overexpression may play an autonomous role in the neoplastic transformation of BALB/c 3T3 cells, as it does in other cell types of mesenchymal origin. Environ. Mol. Mutagen. 41:315,321, 2003. © 2003 Wiley-Liss, Inc. [source] Modulation of VE-cadherin and PECAM-1 mediated cell,cell adhesions by mitogen-activated protein kinasesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2003Jianqiang Wu Abstract Endothelial cell transition from a differentiated, quiescent phenotype to a migratory, proliferative phenotype is essential during angiogenesis. This transition is dependent on alterations in the balanced production of stimulatory and inhibitory factors, which normally keep angiogenesis in check. Activation of MAPK/ERKs is essential for endothelial cell migration and proliferation. However, its role in regulation of endothelial cell adhesive mechanisms requires further delineation. Here, we show that sustained activation of MAPK/ERKs results in disruption of cadherin-mediated cell,cell adhesion, down-regulation of PECAM-1 expression, and enhanced cell migration in microvascular endothelial cells. Expression of a constitutively active MEK-1 in mouse brain endothelial (bEND) cells resulted in down-regulation of VE-cadherin and catenins expression concomitant with down-regulation of PECAM-1 expression. In contrast, inhibition of MEK-1 restored parental morphology, cadherin/catenins expression and localization. These data are further supported by our observation that sustained activation of MAPK/ERKs in phorbol myristate acetate incubated HUVEC lead to disruption of cadherin-mediate cell,cell interactions and enhanced capillary formation on Matrigel. Thus, sustained activation of MAPK/ERKs plays an important role in disruption of cell,cell adhesion and migration of endothelial cells. J. Cell. Biochem. 90: 121,137, 2003. © 2003 Wiley-Liss, Inc. [source] Effects of isorhynchophylline on angiotensin II-induced proliferation in rat vascular smooth muscle cellsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2008Feng Zhang Proliferation of vascular smooth muscle cells (VSMCs) is a crucial event in cardiovascular diseases. Isorhynchophylline, an alkaloid from a traditional Chinese medicine Gambirplant, has been used to treat cardiovascular diseases. The aim of this study was to investigate the effects of isorhynchophylline on angiotensin II (Ang II)-induced proliferation of rat VSMCs. VSMCs were isolated from rat artery and cultured for 14 days before experimentation. The effect of isorhynchophylline on Ang II-induced proliferation was evaluated by cell number, MTT assay and flow cytometry, and nitric oxide (NO) content and activity of NO synthase (NOS) were measured. The expression of proto-oncogene c-fos, osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) mRNAs was measured by real-time RT-PCR. VSMC cultures were verified by morphology and immunostaining with ,-smooth muscle actin. Isorhynchophylline (0.1,10.0 ,M) was not toxic to VSMCs, but markedly decreased Ang II (1.0 ,m)-enhanced cell number and MTT intensity, and blocked cell transition from G0/G1 to S phase. Furthermore, isorhynchophylline increased the NO content and NOS activity, and suppressed Ang II-induced over-expression of c-fos, OPN and PCNA. Thus, isorhynchophylline was effective against Ang-II induced cell proliferation, an effect that appears to be due, at least in part, to increased NO production, regulation of the cell cycle, and depressed expression of c-fos, OPN and PCNA related to VMSC proliferation. [source] Lipid peroxide-induced redox imbalance differentially mediates CaCo-2 cell proliferation and growth arrestCELL PROLIFERATION, Issue 4 2002Yudai Gotoh Dietary oxidants like lipid hydroperoxides (LOOH) can perturb cellular glutathione/glutathione disulphide (GSH/GSSG) status and disrupt mucosal turnover. This study examines the effect of LOOH on GSH/GSSG balance and phase transitions in the human colon cancer CaCo-2 cell. LOOH at 1 or 5 µm were noncytotoxic, but disrupted cellular GSH/GSSG and stimulated proliferative activity at 6 h that paralleled increases in ornithine decarboxylase activity, thymidine incorporation, expression of cyclin D1/cyclin-dependent kinase 4, phosphorylation of retinoblastoma protein, and cell progression from G0/G1 to S. At 24 h, LOOH-induced sustained GSH/GSSG imbalance mediated growth arrest at G0/G1 that correlated with suppression of proliferative activity and enhanced oxidative DNA damage. LOOH-induced cell transitions were effectively blocked by N-acetylcysteine. Collectively, the study shows that subtoxic LOOH levels induce CaCo-2 GSH/GSSG imbalance that elicits time-dependent cell proliferation followed by growth arrest. These results provide insights into the mechanism of hydroperoxide-induced disruption of mucosal turnover with implications for understanding oxidant-mediated genesis of gut pathology. [source] | ||||||||||