Inhibitability apoptosis

Bcl-2 (B-cell lymphoma-related gene) is major mammalian gene that is known to inhibit apoptosis. 

Bcl-x is a gene in the bcl-2 family that inhibits apoptosis after trophic factor deprivation in vitro. 

BID is a member oftheBcl-2 gene family, which encode proteins that function either to promote apoptosis or to inhibit apoptosis as in the proteins derived from Bcl-2. These proteins can exist as monomers or they can dimerize. For example, if two promoting Bcl-2 family proteins dimerize then apoptosis will be greatly enhanced. Conversely, if dimerization of an inhibitory and promotor protein occurs, then the effects are cancelled out. The Bcl-2 family of proteins are localized to the outer mitochondrial or outer nuclear membranes. 

Similar to reactive oxygen species, nitric oxide, peroxynitrite, and other nitrogen oxide species produced by mitochondria are able to stimulate or inhibit apoptosis. Proapoptotic effect of nitric oxide was probably first shown by Albina et al. [138], who demonstrated NO-induced... 

The ability of 3-phosphoinositides to stimulate cell proliferation/survival via activation of Akt is countered by the 3-phosphatase PTEN, which hydrolyzes PI(3,4)P2 and PI(3,4,5)P3. A link between PTEN activity and 3-phosphoinositide content in cells is evident from the observations that (a) overexpression of PTEN results in a dramatic reduction in the cellular content of these lipids, and (b) 3-phosphoinositide concentrations are greatly elevated in mammalian PTEN-null cell lines [28]. Cells in which PTEN activity is reduced have increased tumori-genic properties, since Akt inhibits apoptosis and promotes cell survival. Conversely, PTEN activity programs the fate of the cell toward apoptosis. Mutations of PTEN have been shown to occur in a wide range of tumor types, but with a particularly high frequency in glioblastomas. 

An important animal model of lupus is the lpr mouse. It was discovered that the abnormality leading to autoimmunity in this model is a defect in the gene coding for Fas protein and this leads to impaired apoptosis [103], This, in turn, leads to lymphade-nopathy and prevents elimination of autoimmune T cells, thus interfering with tolerance. Minocycline inhibits apoptosis, and it has been postulated that this contributes to the mechanism of minocycline-induced lupus [104],... 

Beummelkamp, T. R., Nijman, S. M., Dieac, a. M., and Bernards, R. Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB, Nature, 2003, 424, 797-801. 

Alvarez, R.J., Gips, SJ., Moldovan, N., Wilhide, C.C., MiUiken, E.E., Hoang, A.T., Hmban, R.H., Silverman, H.S., Dang, C.V., Goldschmidt-Clermont, P.J., 1997, ITbeta-estradiol inhibits apoptosis of endothelial ceUs, Biochem. Biophys. Res. Commun., 237 372-81... 

Kozawa et al, 2000a and b). In both cell types, the p38 MAPK-specific inhibitor, SB203580, blocks SIP hsp27 induction and amplification of inositol phosphates, hi osteoblastic cells, PGE shmulates cyclic AMP formation and inhibits apoptosis. This appears to be mediated by a cyclic AMP-dependent modulation of SPHK and S IP production (Machwate etal., 1998)... 

Xia, P., Wang, L, Gamble, J.R. and Vadas, M.A., 1999, Activation of sphingosine kinase by tumor necrosis factor-a inhibits apoptosis in human endothelial ceUs, J. Biol. Chem. 274 34499-34505. 

S. Badvie, A. Hanna-Morris, H. J. Andreyev, P. Cohen, S. Saini and T. G. Allen-Mersh, A field change of inhibited apoptosis occurs in colorectal mucosa adjacent to colorectal adenocarcinoma, J. Clin. Pathol., 2006, 59(9), 942. 

Matsuzaki H, TamataniM, MitsudaN, et al. Activation of Akt kinase inhibits apoptosis and changes in B cl- 2 and B ax expres sion induced by nitric oxide in primary hippocampal neurons. J Neu rochem... 

During the process of apoptosis, several mitochondrial proteins are released into the cytoplasm, including AIF and cytochrome C for the activation of proteases (L4). AIF, a tlavoprotein, can induce apoptotic morphological changes of the nucleus in a caspase-independent manner (M7, S8). Cytochrome C probably executes apoptosis by interaction with cytoplasmic protein Apaf-1 and direct activation of caspases (L2). Since the release of AIF and cytochrome C is regulated by the proteins of the Bcl-2 family, Bcl-2 can inhibit apoptosis by retention of cytochrome C in the mitochondria (T6). 

Minocycline is a member of the broad spectrum tetracycline antibiotics. It inhibits apoptosis via attenuation of TNF-alpha and downregulating pro-inflammatory cytokine output. Minocycline is an effective DMARD in patients with early seropositive RA. Pigmentation is a common side effect in patients receiving minocycline therapy for more than 3 months. 

The antiapoptotic members of the Bcl-2 family (Bcl-2, BclX, BclW, Al, Mcl-l) inhibit apoptosis by various cytotoxic effects. At a minimum, they contain the motives BHl and BH2. Bcl-2 protein contains all fom BH motives. For the mechanism of the antiapoptotic function, see 15.3.4 and 15.4. 

These proteins inhibit apoptosis but their site of action is imcertain. Some of them apparently bind to caspases and inhibit these directly. 

Hepatocytes were isolated from male Fischer 344 rats and from three human liver (liver transplantation donors). Treatment with mono(2-ethylhexyl) phthalate induced P-oxidation activity, replicative DNA synthesis and inhibited apoptosis induced by transforming growth factor P (TGFP) in cultured rat but not human hepatocytes (Hasmall et al., 1999). 

Cimmino et al. (40) found that both these miRNAs negatively regulate the expression of B-cell lymphoma 2 (BCL2), which inhibits apoptosis and is present in many types of cancers including leukemias. In fact, overexpression of miR-15 and miR-16 in the MEG-01 cell line induces apoptotic cell death. 

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