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Karin Müller Keri L.H. Carpenter Iain R. Challis Jeremy N. Skepper Mark J. Arends 《Free radical research》2013,47(7):791-802
Epidemiologically, a high-carotenoid intake via a fruit- and vegetable-rich diet is associated with a decreased risk of various forms of cancer. The mechanisms by which carotenoids exert this protective effect are controversial. In this study, we examined the potency of a range of carotenoids commonly found in human plasma to induce apoptosis in Jurkat E6.1 malignant T-lymphoblast cells. At a concentration of 20 w M, the order of potency to induce apoptosis after 24 h was: g -carotene > lycopene > lutein> g -cryptoxanthin=zeaxanthin. Canthaxanthin failed to induce apoptosis under these conditions. g -Carotene induced apoptosis in a time- and concentration-dependent manner with a lowest effective concentration of about 3 w M. Pre-conditioning of g -carotene for 72 h destroyed its pro-apoptotic activity almost completely, whereas degradation for 6 h or less did not, indicating that either g -carotene itself and/or an early degradation product of g -carotene are the death-inducing compounds. Apoptosis induced by g -carotene was characterized by chromatin condensation and nuclear fragmentation, DNA degradation, PARP cleavage and caspase-3 activation. The antioxidant BO-653 inhibited the degradation of g -carotene in vitro and significantly increased its cytotoxicity, indicating that a pro-oxidant effect of g -carotene is unlikely to cause its pro-apoptotic activity. The induction of apoptosis in transformed cells by carotenoids may explain their protective effect against cancer formation in humans. Possible pathways for induction of apoptosis by carotenoids are discussed. 相似文献
83.
Francisco J. Padillo Adolfo Cruz Carmen Navarrete Inmaculada Bujalance Javier Briceño José I. Gallardo 《Free radical research》2013,47(7):697-704
The induction of oxidative stress precedes liver injury during experimental obstructive jaundice (OJ). In this sense, different evidences suggest that melatonin (MEL), as antioxidant, may be useful in the protection against apoptosis and necrosis during experimental cholestasis. In addition, we will also assess if MEL-dependent protection is related to a recovery of antioxidant status disturbances induced by OJ. Cholestasis was achieved by double ligature and sectioning of the principal bile duct. MEL was injected intraperitoneally (500?μg/kg/day). Lipid peroxidation was evaluated by the measurement of malondialdehyde (MDA) content in liver. Different parameters related to antioxidant status, such as reduced glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD) were determined in liver. Liver injury was assessed by alanine aminotransferase (ALT) in serum, histological examination, DNA fragmentation and TUNEL assay. The activation of perisinusoidal stellate cells was evaluated by immunohistochemical measurement of α-smooth muscle actin in liver sections. The induction of OJ increased all the parameters related to apoptosis and necrosis in liver. The induction of liver injury was associated with stellate cell activation, as well as an increase in MDA (p<0.0001) and a reduction in GSH, GPx, catalase and SOD content (p<0.0001) in liver. MEL reduced hepatic apoptosis and necrosis (p<0.004) with a significant improvement in all oxidative stress markers. In conclusion, our results showed that MEL recovered the antioxidant status and reduced apoptosis and necrosis induced by experimental cholestasis. 相似文献
84.
《Journal of receptor and signal transduction research》2013,33(6):359-366
AbstractCongenital Giant Nevi (CGN) are rare melanocytic lesions with the potential to regress into malignant melanoma. Simultaneous up-regulation and cooperative interactions of signaling pathways are crucial events in the pathogenesis of melanocytes. Our study aimed to identify changes in the expression and activation of proteins controlling survival and/or apoptosis of the key signaling pathways PI3K/AKT/BCL2 and Wnt/β-catenin of CGN melanocytes. We applied a model of cultured melanocytes from paired CGN and normal appearing skin, and Western blot (WB) analyzed the expression and activation profile of survival and anti-apoptotic proteins of these signaling pathways, growth pattern, cell cycle and apoptosis. WB analysis demonstrated a significant higher expression level of activated AKT and of BCL2 proteins in the CGN melanocytes compared with paired melanocytes from normal appearing skin. A relative increase in the level of GSK3 and FOXO1 proteins, down stream targets of AKT, as well as of pβ-catenin was also detected in the CGN melanocytes compared with the controls. These changes were not affected by growth of the CGN melanocytes in reduced serum (starvation). Both cell populations shared a similar growth pattern, with no significant differences in the proportion of apoptotic cells and in cell cycle fractions. These data demonstrate for the first time, changes in signaling proteins of cultured CGN melanocytes. Further, suggesting that the changes in AKT/BCL2 signaling molecules might mediate growth and anti-apoptosis processes at least in part, thus increasing the survival potential of CGN melanocytes and maintaining their integrity. 相似文献
85.
《Journal of receptor and signal transduction research》2013,33(3):212-220
AbstractExogenous hydrogen peroxide (H2O2) can easily penetrate into biological membranes and enhance the formation of other reactive oxygen species (ROS). In the present study, we have investigated the neuroprotective effects of insulin on H2O2-induced toxicity of retinoic acid (RA)-differentiated SH-SY5Y cells. To measure the changes in the cell viability of SH-SY5Y cells at different concentrations of H2O2 for 24?h, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT)-based assay was used and a 100?µM H2O2 was selected to establish a model of H2O2-induced oxidative stress. Further assays showed that 24?h of 100?µM H2O2-induced significant changes in the levels of lactate dehydrogenase (LDH), nitric oxide (NO), ROS, and calcium ion (Ca2+) in neuronal cells, but insulin can effectively diminish the H2O2-induced oxidative damages to these cells. Moreover, cells treated with insulin increased H2O2-induced suppression of glutathione levels and exerted an apparent suppressive effect on oxidative products. The results of insulin treatment with SH-SY5Y cells increased the Bcl-2 levels and decreased the Akt levels. The treatment of insulin had played a protective effect on H2O2-induced oxidative stress related to the Akt/Bcl-2 pathways. 相似文献
86.
Y. H. Feng X. Li R. Zeng G. I. Gorodeski 《Nucleosides, nucleotides & nucleic acids》2013,32(9-11):1271-1276
A truncated naturally occurring variant of the human purinergic receptor P2X7 (P2X7-R) was found in human cancer cervical cells. The novel protein consists of 258 amino acids, and compared to the wild-type P2X7-R it lacks the entire intracellular carboxy terminus, the second transmembrane domain, and the distal third of the extracellular loop. The truncated P2X7-R failed to form pores and mediate apoptosis, and it interacted with the wild-type P2X7-R in a manner suggesting auto-hetero-oligomerization. In contrast to cancer cells the novel truncated P2X7-R was expressed relatively little in normal cervical cells. These data raise the possibility that coexpression of the truncated form could block P2X7 mediated apoptosis and promote uncontrolled growth of cells. 相似文献
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88.
Raheleh Halabian Hossein Abdul Tehrani Ali Jahanian-Najafabadi Mehryar Habibi Roudkenar 《Cell stress & chaperones》2013,18(6):785-800
Despite many advantages of mesenchymal stem cells (MSCs) that make them suitable for cell therapy purposes, their therapeutic application has been limited due to their susceptibility to several stresses (e.g., nutrient-poor environment, oxidative stress, and hypoxic and masses of cytotoxic factors) to which they are exposed during their preparation and following transplantation. Hence, reinforcing MSCs against these stresses is a challenge for both basic and clinician scientists. Recently, much attention has been directed toward equipping MSCs with cytoprotective factors to strengthen them against unfavorable microenvironments. Here, we engineered MSCs with lipocalin 2 (Lcn2), a cytoprotective factor that is naturally induced following exposure of cells to stresses imposed by the microenvironment. Lcn2 overexpression not only did not interfere with the multidifferentiation capacity of the MSCs but also granted many protective properties to them. Lcn2 potentiated MSCs to withstand oxidative, hypoxia, and serum deprivation (SD) conditions via antagonizing their induced cytotoxicity and apoptosis. Adhesion rate of MSCs to coated culture plates was also enhanced by Lcn2 overexpression. In addition, Lcn2 induced antioxidants and upregulated some growth factors in MSCs. Our findings suggested a new strategy for prevention of graft cell death in MSC-based cell therapy. 相似文献
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