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EN
Programmed cell death (apoptosis) plays a vital role in the regulation of cellular homeostasis. Because of apoptosis fundamental importance, this process is highly regulated. One important set of factors involved in apoptosis regulation is the Bcl-2 family proteins. Bcl-2 family members form a complex regulatory network that controls cell survival and death in response to different physiological and pathological signals. This family includes both pro- and anti-apoptotic members, and Bax protein (Mol wt 21 kDa) is a major pro-apoptotic factor with multifunctional activity. This review summarizes new data about the main representative of Bcl-2 family – Bax, its structure and mechanism(s) by which this protein modulates apoptosis.
EN
The „changes” occurring in the expression of the factors involved in the apoptotic chain at the level of the respiratory epithelium in asthma is still an unsolved issue. At this level an important role is played by the mitochondria and the factors that influence the membrane permeability, especially the Bcl-2 super family. The purpose of this study is to evaluate both the changes in the expression of the Bcl-2 and of the Bax proapoptotic factors at the respiratory epithelium level in 21 patients with bronchial asthma of different degrees of severity of disease (aaccording to GINA - Global Initiative For Asthma). To accomplish this, fragments of the bronchial mucosa were obtained through fiberbronchoscopy, being afterwords hystologically prepare in view of the immunomarking with anti Bcl-2 and anti-Bax antibodies. Microscopic examination revealed an important decrease in the level of proapoptotic factor Bcl-2 in patients with persistent severe forms of the disease and a significant decrease in the expression of the proapototic Bax factor at the respiratory epithelium level even in the early stages of the disease. Knowing all the factors involved in apoptosis at the respiratory epithelium level in bronchial asthma, as well as of their expression changes will be at the core of new therapeutical approaches to of this disease.
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2003
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vol. 50
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issue 2
389-404
EN
The outer mitochondrial membrane pore (VDAC) changes its structure either voltage-dependently in artificial membranes or physiologically by interaction with the adenine nucleotide translocase (ANT) in the c-conformation. This interaction creates contact sites and leads in addition to a specific organisation of cytochrome c in the VDAC-ANT complexes. The VDAC structure that is specific for contact sites generates a signal at the surface for several proteins in the cytosol to bind with high capacity, such as hexokinase, glycerol kinase and Bax. If the VDAC binding site is not occupied by hexokinase, the VDAC-ANT complex has two critical qualities: firstly, Bax gets access to cytochrome c and secondly the ANT is set in its c-conformation that easily changes conformation into an unspecific channel (uniporter) causing permeability transition. Activity of bound hexokinase protects against both, it hinders Bax binding and employs the ANT as anti-porter. The octamer of mitochondrial creatine kinase binds to VDAC from the inner surface of the outer membrane. This firstly restrains interaction between VDAC and ANT and secondly changes the VDAC structure into low affinity for hexokinase and Bax. Cytochrome c in the creatine kinase complex will be differently organised, not accessible to Bax and the ANT is run as anti-porter by the active creatine kinase octamer. However, when, for example, free radicals cause dissociation of the octamer, VDAC interacts with the ANT with the same results as described above: Bax-dependent cytochrome c release and risk of permeability transition pore opening.
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