Effect of mitogens

Continuous cell division is foimd, for example, in stem cells, which serve as precursors for other cells, and in tissue in which dying cells must be replaced. This requires the continuous effects of mitogenic signals. In this case, cell division must ensme homeostasis of the cell structure or the tissue. An increase in the cell number through cell division compensates for loss of cells that die as a part of normal cell turnover or that are eliminated by programmed cell death, or apoptosis. 

Effects of Mitogen-Activated Protein Kinases on T Cells... 

Shen G, Hebbar V, Nair S, Xu C, Li W, Lin W, Keum YS, Han J, Gallo M A, Kong AN. 2004. Regulation of Nrf2 transactivation domain activity. The differential effects of mitogen-activated protein kinase cascades and synergistic stimulatory effect of Raf and CREB-binding protein. J Biol Chem 279 23052-23060. 

Therefore, polyphenols can interfere with intracellular signaling cascades that mediate the effects of mitogenic stimuli by modulating the activity of several kinases. ERKl/2, PI3K, and phosphorylated Akt levels are mainly affected, as well as phosphorylation of INK and MAPK p38 protein levels. Subsequently this modulation leads to reduced activation of transcription factors and induction of growth arrest or apoptosis (Fig. 3). 

Finally, in another study related to nutrition and the immune response in the aged, old mice were given oral doses of two amino acids (qv), lysine and arginine. The treated mice showed evidences of recovered mitogenic responsiveness, expression of T-ceU markers, and production of thymic semm factor (thymulin). The effect of the amino acid combination, sold commercially as Neoiodarsolo, seems to consist mainly of the reactivation of the... 

Fluorid ions stimulate bone formation by a direct mitogenic effect on osteoblasts mediated via protein kinase activation and other pathways. Further to these cellular effects, fluorides alter hydroxyapatite crystals in the bone matrix. In low doses, fluorides induce lamellar bone, while at higher doses abnormal woven bone with inferior quality is formed. The effect of fluorides on normal and abnormal (e.g. osteoporotic) bone therefore depends on the dose administered. 

Activation of Mi, M3, and M5 mAChRs does not only lead to the generation of IP3 followed by the mobilization of intracellular Ca2+, but also results in the stimulation of phospholipase A2, phospholipase D, and various tyrosine kinases. Similarly, M2 and M4 receptor activation does not only mediate the inhibition of adenylyl cyclase, but also induces other biochemical responses including augmentation of phospholipase A2 activity. Moreover, the stimulation of different mAChR subtypes is also linked to the activation of different classes of mitogen-activated protein kinases (MAP kinases), resulting in specific effects on gene expression and cell growth or differentiation. 

To ensure that the inhibition of EGF binding by palytoxin was not a consequence of cell toxicity, the effect of palytoxin on DNA synthesis in Swiss 3T3 cells was monitored. When cells were incubated in the presence of palytoxin, 10% fetal calf serum, and H-thymidine for 19.5 hr, no depression in the extent of H-thymidine incorporation into DNA was detected up to 3.7 pM palytoxin (Table I). Although 11 pM palytoxin was toxic when present for a prolonged period, under the conditions of the assays described above no toxicity was detected (Table I). When cells were incubated in the presence of palytoxin, 0.1% fetal calf serum, and H-thymidine, palytoxin did not stimulate significant incorporation of H-thymidine into DNA. Thus, although it can modulate the EGF receptor system under these conditions, palytoxin alone does not appear to be mitogenic for Swiss 3T3 cells. 

Figure 4 Effect of neutral oligosaccharide-alditol fractions derived from PG-lc by lithium degradation on mitogenic activity of PG-lc...

Goligorsky, M.S., Morgan, M.A., Suh, H., Safirstein, R and Johnson, R (1992). Mild oxidative stress, cellular mode of mitogenic effect. Renal Failure 14, 385-389. 

The biochemical mechanism of Mos action is not yet established. Mos has been found to phosphorylate cyclin B in vitro, and it is possible that this phosphorylation directly inhibits cyclin B proteolysis (Roy et al., 1990). However, such a direct effect of phosphorylation on cyclin B stability remains to be demonstrated, and it is alternatively possible that Mos inhibits (directly or indirectly) the proteolytic pathway responsible for cyclin B degradation. Mos has recently been found to stimulate mitogen-activated protein kinase (MAP kinase) in Xenopus oocytes,... 

Ghanmi, Z., M. Rouabhia, O. Othmane, and P.A. Deschaux. 1989. Effects of metal ions on cyprinid fish immune response in vitro effects of Zn2+ and Mn2+ on the mitogenic response of carp pronephros lymphocytes. Ecotoxicol. Environ. Safety 17 183-189... 

Investigations of the cellular effects of radiofrequency radiation provide evidence of damage to various types of avian and mammalian cells. These effects involve radiofrequency interactions with cell membranes, especially the plasma membrane. Effects include alterations in membrane cation transport, Na+/K+-ATPase activity, protein kinase activity, neutrophil precursor membrane receptors, firing rates and resting potentials of neurons, brain cell metabolism, DNA and RNA synthesis in glioma cells, and mitogenic effects on human lymphocytes (Cleary 1990). 

Experimental studies showed antitumoral effects of raloxifene in different in vitro preparations and animal models. Raloxifene has been able to inhibit the mitogenic effect induced by estrogens on ZR-75-1 cells, an estrogen responsive human breast cancer cell line (Poulin et al. 1989). In a well-accepted rat model of breast cancer induced by nitroso-methyl urea (NMU) raloxifene significantly suppressed the development of breast tumors and acted synergistically with 9 cis-retinoic acid (Anzano et al. 1996). 

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