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    3-AMINOBENZAMIDE PROTECTS CELLS FROM UV-B-INDUCED APOPTOSIS BY ACTING ON CYTOSKELETON AND SUBSTRATE ADHESION

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    3-aminobenzamide (3-ABA) is an inhibitor of poly-(ADP-ribose)-polymerase, an enzyme involved in numerous subcellular processes, including cell death. Recently, a target effect of the drug on some cytoskeletal elements has also been described (Malorni et al., Biochem. Biophys. Res. Commun. 202: 915-922, 1994). In this study we evaluated the ability of 3-ABA to interfere with UV-B ray-induced apoptosis in cells selected for their cytoskeletal features and their different capability to adhere to the substrate. Human melanoma (M14) and epithelial (A431) cell lines and murine primary fibroblastic cultures (MFC) were studied. Our results indicate that cytoskeleton is indeed an important cellular target of 3-ABA, which can prevent apoptotic cell death by UV-B through a specific effect on the adhesion properties of the cells. indeed, an inverse correlation was observed between sensitivity to UV-B-induced apoptosis (M14>A431>MFC) and substrate adhesion (MFC>A431>M14). The potential relevance of these observations to understand the possible relationships among apoptosis, cytoskeletal functions and substrate adhesion is discussed

    CELL-DEATH PROTECTION BY 3-AMINOBENZAMIDE AND OTHER POLY(ADP-RIBOSE)POLYMERASE INHIBITORS - DIFFERENT EFFECTS ON HUMAN NATURAL-KILLER AND LYMPHOKINE-ACTIVATED KILLER-CELL ACTIVITIES

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    The death of target cells by cytotoxic effector cells is a relevant biological phenomenon, where cells are activated and a very quick apoptotic program occurs. In order to test the hypothesis that the nuclear enzyme poly(AD P-ribose)polymerase (PADPRP) plays a role in such a process, a variety of PADPRP inhibitors such as 3-aminobenzamide, nicotinamide, 4-aminobenzamide and luminol were used. All of them were able to strongly inhibit K562 target cell killing by human effector natural killer cells (NK) in a 4hr Cr-51 release assay. PADPRP inhibitors were much less effective in protecting target cells when lymphokine activated killer cells (LAK) were used as effecters. These substances were active only when both target and effector cells were mixed, being ineffective on target or effector cells alone. On the whole, these data indicate that PADPRP is involved in the death of target cells. Moreover, the different sensitivity of NK and LAK activities to PADPRP inhibitors suggests that the molecular mechanisms underlying these two types of cytotoxicity are at least partially different

    Age related changes in lipid secretion by perfused livers of Wistar rats.

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    Male Wistar rats show typical age-related variations in the distribution of high-density lipoprotein subfractions that include an increase in HDL1 and a decrease in HDL2 proportion. The role of liver in these variations was evaluated by studying the lipoprotein and bile secretions from perfused livers of 14± 1 and 3.5±0.5 month old Wistar rats (adult and young animals, respectively). The lipid content of lipoproteins secreted from adult livers was higher in HDL2 fraction and lower in VLDL fraction. The lipid output did not show significant age-related variations in the case of HDL1 fraction. However, the lipoproteins secreted from adult livers contained a higher proportion of phospholipids, and a lower proportion of triacylglycerols in comparison with lipoproteins secreted by young livers. Therefore, the molar ratio of core to surface lipids was lower in lipoproteins secreted by adult livers. Adult livers showed a reduction in bile flow by about 37% with a significantly higher phospholipid secretion. These findings suggest that both the hepatic metabolism of glycerophospholipids and their repartition between plasma and bile compartments are affected by aging process. In conclusion, present data show that the age-related increase in plasma HDL1 proportion, previously observed in this rat strain in vivo, are not due to a higher liver secretion of these particles. Conversely, liver appears to have a major role in the age-related VLDL increase and in the variations of phospholipid lipoprotein secretion

    CELL-DEATH PROTECTION BY 3-AMINOBENZAMIDE - IMPAIRMENT OF CYTOSKELETON FUNCTION IN HUMAN NK CELL-MEDIATED KILLING

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    3-aminobenzamide, an inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase, is capable of interfering with the tumor cell lysis induced by specialized cells from the immune system, i.e., natural killer (NK) cells. In this report we suggest that the mechanism by which the drug can exert its protective effects on target cell killing by NK effectors can also be due to its ability to impaire cell-to-cell conjugate formation (binding), without affecting either the expression of cell adhesion molecules nor the features of effector-target cell contact. The mechanism of this inhibition seems to be associated with an alteration of cytoskeletal elements involved during conjugate formation, i.e. with the integrity and function of the microfilament system

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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