Journal Of Endocrinology And Metabolism

This allows other downstream events such as activation of ERK and caspase to take place upon TCR engagement.The maintenance of both intra and extracellular reducing conditions is a prerequisite for the proper functioning of T lymphocytes.Normally, T cells control the intracellular redox balance through various cytosolic antioxidant systems.However, the T cell microenvironment is always pushed to oxidation by various factors, one of which is the production of ROS by neutrophils and macrophages at the site of inflammation. It has been estimated that in the microenvironment of these cells the concentration of hydrogen peroxide can reach M. This oxidative milieu can become chronic if inflammation persists and macrophages and neutrophils are continuously recruited.The generation of an oxidative environment has a strong influence on T lymphocytes.It has been shown that T cells isolated from patients affected with rheumatoid arthritis, cancer, leprosis, or AIDS show altered functional properties. Previous in vitro work on the effects of oxidative stress on T lymphocytes showed that ROS induce T cell hyporesponsiveness and alter the expression levels of key T cellsignaling molecules such as TCR or plck. Interpretation of these results is made difficult by the high doses of exogenously added hydrogen peroxide utilized. To circumvent this problem, we established an in vitro system in which freshly isolated T cells are rendered hyporesponsive by exposing them to oxidative stress generated by activated syngenic neutrophils.We showed that RA SF neutrophils can induce T cell hyporesponsiveness ex vivo by secreting HO.Blots were reblotted with antiTCR antibodies, respectively.A representative result of four independent experiments is shown.PLC activation was quantified by densitometry analysis and expressed as the percentage of PPLCPLC. In contrast to PLC, TCR signaling led to increased ERK activation in normal and hyporesponsive T cells.It has recently been shown that mild oxidative stress activates other MAP kinasesignaling pathways other than ERK. It has recently been reported that caspase activation is a necessary event for normal T cell activation. Although the ultimate effects of caspase activation during T cell responses are unknown, this result suggests that certain effector functions may be maintained in hyporesponsive T cells.The fact that caspase cleavage is not observed in unstimulated hyporesponsive T cells further supports the validity of our in vitro system and its relevance for human pathology.The results reported here uncover the divergent effects of ROS on T cellsignaling pathways.Blood. jbc.M When a correction for this article is posted Click here to choose from all of JBCs email alerts This article cites references, of which can be accessed free at http:www.jbc.orgcontent.full.htmlreflist Downloadedfromhttp: www.jbc.orgbyguestonSeptember, The recent demonstration of an intrinsic deoxyribosephosphate lyase activity in pol supports a function of this enzyme in base excision repair.However, the biochemical properties of the polymerization activity of this enzyme are still largely unknown.We have cloned and purified human pol to homogeneity in a soluble and active form, and we present here a biochemical description of its polymerization features.In support of a role in DNA repair, pol inserts nucleotides in a DNA templatedependent manner and is processive in small gaps containing a phosphate group.

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