Cellular apoptosis

To characterize phospholipid oxidation during apoptosis, cellular phospholipids were metabolically labeled at sn-2 position with a natural unsaturated florescent fatty acid containing four conjugated double bonds, cw-parinaric acid (cw-PnA) (Kagan et al, 1998 Tyurina et al, 2001). Oxidative desttuction of any part of the conjugated double bond system of... 

One class of signaling pathways that has received considerable attention involves the action of cytokine-stimulated sphingomyelinase (SHM-ase) (Hannun and Obeid, 1997). Ceramide generated from SHM-ase activation plays a critical role in cytokine-mediated apoptosis, cellular differentiation, and senescence, each of which may be important in the inflammatory response. 

In this type of reaction an antigen elicits the generation of cytotoxic T-lymphocytes ( immune defense). Cytotoxic T-lymphocytes (Tc) destroy antigen bearing cells by inducing apoptosis. This reaction can be viewed as the cellular counterpart to the humoral Type II reactions. They play an important physiological role in the defense of viruses, and can become allergic reactions under the same conditions as described for Type II reactions. 

Decitabine (5-aza-deoxycytosine) is an analog of the nucleoside 2 -deoxycytidine. It is believed to exert its antineoplastic effects after phosphorylation and direct incorporation into DNA and by inhibition of the enzyme DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation or apoptosis. DNA hypomethylation is achieved at concentrations below those required to significantly inhibit DNA synthesis, which may promote restoration of function to genes associated with control of cellular differentiation and proliferation. Cytotoxicity in rapidly dividing cells may also result from covalent adducts between DNA methyltransferase and decitabine. 

Oblimersen sodium is a DNA antisense oligonucleotide designed to specifically bind to human bcl-2 mRNA, resulting in catalytic degradation of bcl-2. This results in decreased translation of the protein Bcl-2, which is a cellular antiapoptotic protein. Thus, oblimersen enhances sensitivity to chemotherapy by shifting the intracellular balance to a state in which the cells are more likely to be killed by apoptosis. Currently, it is used in combination chemotherapy for treating advanced melanoma. 

The CaR regulates numerous biological processes, including the expression of various genes (e.g., PTH) the secretion of hormones (PTH and calcitonin), cytokines (MCP-1), and calcium (e.g., into breast milk) the activities of channels (potassium channels) and transporters (aquaporin-2) cellular shape, motility (of macrophages), and migration cellular adhesion (of hematopoietic stem cells) and cellular proliferation (of colonocytes), differentiation (of keratinocytes), and apoptosis (of H-500 ley dig cancer cells) [3]. 

The pro- and antiapoptotic members of the Bcl2 family affect cellular sensitivity to apoptosis and thus to many chemotherapeutic agents [4]. For example, overexpression of the antiapoptotic genes Bcl2 and Bcl-XL in some cell lines and tumors can confer resistance to apoptosis triggered by ionizing radiation. Conversely, overexpression of proapoptotic Bax in experimental tumors can induce apoptosis directly or render such tumors more sensitive to cisplatin and 5-FU. 

Cell Cycle Control. Figure 3 The DNA damage checkpoint. In response to DNA damage cells activate p53 dependent and independent checkpoint pathways leading to cell cycle arrest at G1/S and G2/M allowing DNA repair. If the cellular damage cannot be repaired, cells can initiate apoptosis. 

Other, more general effects of insulin on cellular function include stimulation of cell growth (increase in DNA and protein synthesis), inhibition of apoptosis, and modulation of ion-channel activity. 

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