Cell survival development

Neurotrophins are peptides or protein molecules that regulate both cell survival and cell death of specific neuronal phenotypes and thus serve to influence development, maintenance, function, and plasticity of the nervous system. 

Booth V Keizer DW, Kamphuis MB et al (2002) The CXCR3 binding chemokine IP-IO/CXCLIO structure and receptor interactions. Biochemistry 41 10418-10425 Burns JM, Summers BC, Wang Y et al (2006) A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med 203 2201-2213 Callebaut C, Krust B, Jacotot E et al (1993) T cell activation antigen, CD26, as a cofactor for entry of HIV in CD4+ cells. Science 262 2045-2050... 

Knapp PE, Itkis OS, Zhang L, Spruce BA, BakaUdn G, Hauser KF (2001) Endogenous opioids and oligodendroglial function possible autocrine/paracrine effects on cell survival and development. Glia 35 156-165... 

Bums JM, Summers BC, Wang Y, et al. A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med 2006 203 2201-2213. 

IFN-y also directly modulates the immune response by affecting growth, differentiation and function of both T- and B-lymphocytes. These effects are quite complex and are often influenced by additional cytokines. IFN-y acts as a growth factor in an autocrine manner for some T cell sub-populations, and it is capable of suppressing growth of other T cell types. It appears to have an inhibitory effect on development of immature B-lymphocyte populations, but it may support mature B cell survival. It can both up-regulate and down-regulate antibody production under various circumstances. 

IBDNF Neive growth factor Neuronal development Cell survival Mood enhancer... 

There is a family of proteins (the Bcl-2 family) that can regulate the potential across the inner mitochondrial membrane, and its permeability. Hence, they can influence apoptosis. Some of this family stabilise the inner membrane and maintain the potential, so that they suppress apoptosis. They are known as cell survival molecules (e.g. the proteins, Bcl-2, Bcl-X). Other members of the family destabilise the mitochondria and decrease the membrane potential which facilitates apoptosis. They are known as cell killer proteins (e.g. the proteins, Bax, Bak). The mechanisms by which they have their effects on mitochondria are not known. They are, of course, of considerable interest for the development and control of growth of tumour cells (See Chapter 21). 

The methylation of DNA at CpG islands has also turned out to be an important regulator for cell development, the differentiated proteome and the regulation of cell survival [237,238]. Indeed the implications of this chemical modification have been linked to DNA accessibility, chromatin fluidity and cell transformation [239,240]. DNA methylation is required for genomic stability and believed to act as an inert epigenetic marker in germinal cells and preimplantation embryos [238]. Presumably, DNA methylation is required for the heritable transmission of chromatin structure, which prevents the expression of terminally silenced genes in differentiated tissues, and provides a host-defense mechanism against parasitic transposable elements [241]. 

Knowledge of the mechanisms whereby the amino acid transmitters produce their effects has been valuable in the development of psychotropic drugs that may improve memory, reduce anxiety, or even counteract the effects of post-stroke hypoxia on brain cell survival. Some of these aspects are considered later. 

Zeng H, Qian Z, Myers MP, Rosbash M 1996 A light-entrainment mechanism for the Drosophila circadian clock. Nature 380 129-135 Zilian O, Frei E, Burke R et al 1999 double-time is identical to discs overgrown, which is required for cell survival, proliferation and growth arrest in Drosophila imaginal discs. Development 126 5409-5420... 

The MTT assay was initially developed as a quantitative assay for cell survival and proliferation, not as an in vitro assay for chemosensitivity testing. Further study was required to ascertain if the method accurately predicted the in vivo antitumor activities of anticancer agents. Shimoyama et al. [189] studied the predictability of the MTT assay with respect to a clonogenic assay (Sect. 4.1.1.3.) and showed excellent reproducibility and a close correlation to the in vivo predictability rate of the clonogenic assay. Another study [190] also showed that the MTT assay closely approximated (90%) the clinical activity of anticancer agents. Many authors have since utilized the MTT assay to determine the efficacy of polymeric anticancer drug conjugates. 

Apoptosis is attributed a central importance in homeostasis of tissues in an organ or a tissue, the cell number must be kept constant within narrow limits. An increase in cells due to cell division is compensated by processes to eliminate cells that are no longer functional or are old. Apoptosis is a process that helps to keep the cell number in a tissue within limits that are suitable for the development and function of the organism. If defects occur in the apoptotic program, the consequence may be a pathologic increase or decrease in cells (Fig. 15.2). Examples of diseases associated with an increased rate of cell survival are cancer and autoimmune diseases. Diseases associated with increased apoptosis include AIDS and neurodegenerative diseases (Thompson, 1995). 

Activation energies are energy barriers to chemical reactions. These barriers are crucial to life itself. The rate at which a molecule undergoes a particular reaction decreases as the activation barrier for that reaction increases. Without such energy barriers, complex macromolecules would revert spontaneously to much simpler molecular forms, and the complex and highly ordered structures and metabolic processes of cells could not exist. Over the course of evolution, enzymes have developed lower activation energies selectively for reactions that are needed for cell survival. 

The chemical repair rates for the survival of V70 cells and two typical lesions, DSBs and SSBs are shown in Table 12.19. There is no difference between cell survival and DSB formation when the large error bars are taken into account. In contrast, the repair rate for SSBs is much slower. This difference may be accounted for on the basis of the clustered lesion model (Sect. 12.5) considering that if one of two precursors of nearby SSBs has been successfully repaired, a DSB can no longer develop. Note that the probability of one or the other of these radicals being chemically repaired is twice that of a that of an SSB free-radical precursor. 

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