Effects Of Sodium Orthovanadate On And Its Mechanisms In The Regulation Of Proliferation, Cell Cycle Status And Apoptosis In Raji Cells

Objective : Apoptosis ( sometimes termed cell suicide or programmed cell death, PCD) is a highly regulated form of cell death characterized by distinct morphological and biochemical features, in which the cell actively uses a genetically controlled program to cause its own dismantling . Apoptosis is now recognized as a key regulatory process in biology. It is the mode of the cell death that allows the elimination of damaged , senescent , transformed and mutated or unwanted cells in multicellular organisms, without (or with only a minimal) damage to the microenvironment and inflammation. It plays a complementary but opposite role to mitosis or proliferation, and is essential for the maintenance of tissue homeostasis and balance in the kinetics of cell population, as well in embryologic development as in a variety of physiological functions and pathological reactions of adult tissues, organs and organisms. Recent evidence suggests that disturbances in the regulation of apoptosis contribute to the pathogenesis of a number of human diseases. Inappropriate Inhibition of apoptosis is associatedwith malignancies, autoimmune disorders and persistence of viral infections. Overdue apoptosis is part of pathogenetic mechanisms in AIDS, neuro-degenerarive disorders, ischemic injury and toxin-induced organ-specific diseases. Apoptosis can be induced by diverse apoptotic stimuli of either physiological stresses or pathological insults which via signaling transduction pathways, converge on a common apoptotic cell death effecter mechanism consisting essentially of effectors molecules(caspases), adaptor molecules (Apaf-1), and regulatory molecules[pro- and antiapoptotic Bcl-2 family members, inhibitors of apoptosis(IAPs), and Smac/ DIABLO]. In this intricate, but well-organized system the mitochondrion is an integrator of cell death machinery. In response to multiple apoptotic signals of different origins , the outer mitochondrial membrane is permeabilized , resulting in the release to the cytosol of molecules (for example, cytochrome c, Smac/DIABLO) that are crucial for the activation of downstream effectors of apoptosis. Once caspases are activated, they cleave substrate proteins, which will ultimately lead to the morphological manifestations of apoptosis, such as membrane blebbing , and DNA condensation and fragmentation. There is evidence that a diversity of signal transduction pathways are definitely implicated in apoptosis and proliferation, including protein tyrosine kinases(PTKs), steroid receptors, ceremide, inositol phosphates, death receptors (FasL/Fas, TNF- a /TNFR), cytokinereceptors themselves and several proteins such as FADD, RIP and TRADD that interact with the cytoplasmic "death domain" of CD95(Fas) and TNF receptors (p55TNF-Rl and p75TNF-R2) . Among those signal transduction pathways involved in the apoptosis and proliferation tyrosine phosphorylation of proteins plays a key and universal role in the signal transduction of many vital cellular processes including apoptosis , proliferation and cell cycle regulation. The intra-cellular level of protein tyrosine phophorylation depends largely upon both the activity of PTKs and that of protein tyrosine phosphatases ( PTPases) which can specifically hydrolyze phosphorus group at phosphorylated tyrosine residues. Evidence from many researches is emerging that PTPases are, like PTKs, involved in many such critical cellular aspects as proliferation, differentiation, apoptosis, adhesion, and migration. Although tremendous progress has been achieved in our understanding of the roles which PTKs play in and the underlying mechanisms via which they exert on such cellular activities as those listed previously, much little is known about PTPases concerned with these issues and the conclusions from different observers were elusive and sometimes paradoxical. It remains to be determined whether or not PTPases play just an opposite role to PTKs in such cellular processes as proliferation, apoptosis, and cell cycle status or if they do share some identical or overlappin...