Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Dec 2004
Alterations in protein expression in HL-60 cells during etoposide-induced apoptosis modulated by the caspase inhibitor ZVAD.fmk.
DNA topoisomerase inhibitors induce a specific signaling cascade that promotes an active apoptotic caspase-dependent cell death process. However, little is known about the initial signals elicited by these agents. In the present study, we compared apoptosis in HL-60 cells treated either with the chemotherapeutic drug etoposide (VP16) alone or combined with the broad caspase inhibitor ZVAD.fmk. ⋯ Indeed, some proteins were induced in the cytoplasm and subsequently accumulated in the nuclei after etoposide treatment. This process was slightly inhibited by the caspase inhibitor ZVAD.fmk. We suggest that these proteins are associated with the induction of specific signaling cascades that characterize the apoptotic cell death process.
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Ann. N. Y. Acad. Sci. · Dec 2004
Role of constitutively activated and insulin-like growth factor-stimulated ERK1/2 signaling in human hepatoma cell proliferation and apoptosis: evidence for heterogeneity of tumor cell lines.
Enhanced insulin-like growth factor II (IGF-II) and type I IGF receptor (IGF-IR) gene expression in liver tumors and the development of liver tumors in transgenic mice overexpressing IGF-II in the liver suggest that the IGFs and underlying signaling cascades may play auto/paracrine roles in the control of hepatocarcinoma (HCC) cell proliferation and in their protection against apoptosis. We have focused on the role of mitogen-activated protein kinase (ERK1/2) signaling on human HepG2 and Huh-7 hepatoma cell proliferation and on the protection of these cells against drug-induced apoptosis. Physiological concentrations of IGF-I stimulated DNA replication in HepG2 cells (1.5-fold) but not in Huh-7 cells, and this effect was abolished by PD98059 (MEK-1 inhibitor). ⋯ We have shown that drug treatment enhanced (17-fold) or did not modify constitutive ERK1/2 activity in cultured HepG2 or Huh-7 cells, respectively. In both cell lines, inhibition of constitutive and drug-induced ERK1/2 activity by PD98059 yielded a complete inhibition of drug-induced apoptosis. Altogether, our data demonstrate the heterogeneous response of human hepatoma cells to an IGF stimulus and suggest (1) that auto/paracrine effects of IGF-I/-II might contribute to the proliferation of HCC cells and to their protection against apoptosis in vivo and (2) that drug-induced activation of ERK1/2 plays a role in drug-induced apoptosis in human hepatoma cells.
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Ann. N. Y. Acad. Sci. · Dec 2004
Early events in antigen-specific regulatory T cell induction via nasal and oral mucosa.
Mucosal Tr prevent harmful immune responses to innocuous antigens that are encountered at the mucosae. This unique subset of Tr is adaptive, antigen specific, and suppresses irrespective of cytokine polarization. Here we study the earliest events of mucosal Tr induction and factors that control their differentiation from naive T cells.
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Ann. N. Y. Acad. Sci. · Dec 2004
Can posttraumatic stress disorder be prevented with glucocorticoids?
Patients with critical illness who are treated in an intensive care unit (ICU) often report traumatic memories from ICU treatment, receive exogenously administered glucocorticoids for medical reasons, and have a relatively high incidence of chronic stress symptoms and posttraumatic stress disorder (PTSD) during follow-up. ICU therapy could therefore represent a useful model for investigating glucocorticoid effects on traumatic memories and PTSD development. Studies in long-term survivors of ICU treatment demonstrated a clear and vivid recall of different categories of traumatic memory such as nightmares, anxiety, respiratory distress, or pain. ⋯ The prolonged administration of glucocorticoids (stress doses of hydrocortisone) to critically ill patients resulted in a significant reduction of PTSD symptoms measured after recovery without influencing the number of categories of traumatic memory. This protective effect of cortisol can possibly be explained by a cortisol-induced temporary impairment in traumatic memory retrieval which has previously been demonstrated in both rats and humans. Therefore, stress doses of hydrocortisone could be useful for prophylaxis and treatment of PTSD.
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Ann. N. Y. Acad. Sci. · Dec 2004
Oxidative stress and changes in alpha- and gamma-tocopherol levels during coronary artery bypass grafting.
We studied whether cardiopulmonary bypass (CPB) has any immediate impact on the initiation of antioxidative defenses in the body by measuring F(2)-isoprostanes and alpha- and gamma-tocopherol, respectively. 8-iso-PGF(2alpha) levels increased significantly within 3 minutes and until the end of CPB. alpha-Tocopherol levels increased gradually at 20 min during CPB and continued until 6 hours after CPB. gamma-Tocopherol levels followed a similar fashion at the end of CPB. 8-iso-PGF(2alpha) and tocopherol levels kept at basal level 12 and 24 hours post CPB. These findings suggest that an increased free radical-induced oxidative stress together with a gradual appearance of antioxidative defense system during and after CPB.