17β-estradiol abrogates apoptosis inhibiting PKCδ, JNK and p66Shc activation in C2C12 cells

17β-Estradiol (E2) protects several non-reproductive tissues from apoptosis, including skeletal muscle. Previously, we showed that E2 at physiological concentrations prevented apoptosis induced by H2O2 in skeletal myoblasts. As we have also demonstrated a clear beneficial action of this hormone on skeletal muscle mitochondria, the present work further characterizes the signaling mechanisms modulated by E2 that are involved in mitochondria protection, which ultimately result in antiapoptosis. Here, we report that E2 through estrogen receptors (ERs) inhibited the H2O2-induced PKCδ and JNK activation, which results in the inhibition of phosphorylation and translocation to mitochondria of the adaptor protein p66Shc. In conjunction, the inhibition by the hormone of this H2O2-triggered signaling pathway results in protection of mitochondrial potential membrane. Our results provide basis for a putative mechanism by which E2 exerts beneficial effects on mitochondria, against oxidative stress, in skeletal muscle cells. J. Cell. Biochem. 116: 1454-1465, 2015.Fil: la Colla, Anabela Belén. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico Bahia Blanca. Instituto de Ciencias Biologicas y Biomedicas del Sur; ArgentinaFil: Boland, Ricardo Leopoldo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico Bahia Blanca. Instituto de Ciencias Biologicas y Biomedicas del Sur; ArgentinaFil: Vasconsuelo, Andrea Anahi. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico Bahia Blanca. Instituto de Ciencias Biologicas y Biomedicas del Sur; Argentin

The relationship of the perceived impact of the current Greek recession with increased suicide risk is moderated by mental illness in patients with long-term conditions

Objective: Adverse life events may contribute to the emergence of suicidality. We aimed to test the relationship between the impact of the Greek recession and suicidal risk in people with long-term conditions (LTCs) and to determine whether this relationship is moderated by the presence of a mental disorder. Methods: Suicidal risk (RASS) and crisis parameters were assessed in a cross-sectional survey including 376 patients with LTCs (type-II diabetes mellitus, rheumatological disorders and chronic obstructive pulmonary disease) attending the Emergency Department or specialty clinics. A diagnosis of mental disorder was confirmed by the Mini International Neuropsychiatric Interview (MINI) interview. Hierarchical regression models were used to quantify moderator effects. Results: Suicidal risk was significantly associated with the perceived impact of the recession (p = 0.028). However, moderation analysis showed that this relationship was significant only in those diagnosed with either major depressive disorder or generalized anxiety disorder. Conclusions: These findings suggest that the perceived impact of the current Greek recession is not correlated with suicidal risk per se, but the recession may act as precipitator in combination with other risk factors, such as the presence of a mental illness, thus supporting the importance of early diagnosis and treatment of mental disorders in vulnerable groups

Berberine enhances inhibition of glioma tumor cell migration and invasiveness mediated by arsenic trioxide

<p>Abstract</p> <p>Background</p> <p>Arsenic trioxide (As₂O₃) exhibits promising anticarcinogenic activity in acute promyelocytic leukemic patients and induces apoptosis in various tumor cells <it>in vitro</it>. Here, we investigated the effect of the natural alkaloid berberine on As₂O₃-mediated inhibition of cancer cell migration using rat and human glioma cell lines.</p> <p>Methods</p> <p>The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to determine the viability of rat C6 and human U-87 glioma cells after treatment with As₂O₃or berberine, and after co-treatment with As₂O₃and berberine. The wound scratch and Boyden chamber assays were applied to determine the effect of As₂O₃and berberine on the migration capacity and invasiveness of glioma cancer cells. Zymography and Western blot analyses provided information on the effect of As₂O₃and berberine on the intracellular translocation and activation of protein kinase C (PKC), and some PKC-related downstream factors. Most assays were performed three times, independently, and data were analyzed using ANOVA.</p> <p>Results</p> <p>The cell viability studies demonstrated that berberine enhances As₂O₃-mediated inhibition of glioma cell growth after 24 h incubation. Untreated control cells formed a confluent layer, the formation of which was inhibited upon incubation with 5 μM As₂O₃. The latter effect was even more pronounced in the presence of 10 μM berberine. The As₂O₃-mediated reduction in motility and invasion of glioma cells was enhanced upon co-treatment with berberine. Furthermore, it has been reported that PKC isoforms influence the morphology of the actin cytoskeleton, as well as the activation of metalloproteases MT1-MMP and MMP-2, reported to be involved in cancer cell migration. Treatment of glioma cells with As₂O₃and berberine significantly decreased the activation of PKC α and ε and led to actin cytoskeleton rearrangements. The levels of two downstream transcription factors, myc and jun, and MT1-MMP and MMP-2 were also significantly reduced.</p> <p>Conclusion</p> <p>Upon co-treatment of glioma cells with As₂O₃and berberine, cancer cell metastasis can be significantly inhibited, most likely by blocking the PKC-mediated signaling pathway involved in cancer cell migration. This study is potentially interesting for the development of novel chemotherapeutic approaches in the treatment of malignant gliomas and cancer development in general.</p

Upregulation of PKC δ- and downregulation of PKC α-mRNA and protein by a phorbol ester in human T84 cells

AbstractProtein kinase C (PKC) family members are downregulated by chronic activation at the protein level in most cell types. In T84 human epithelial cells 12-O-tetradecanoyl phorbol 13-acetate (TPA) caused persistent translocation of PKC δ to the membrane compartment and a 400% increase of PKC δ-mRNA after 24 h. In contrast, PKC α protein was completely downregulated and its mRNA was decreased to 60% of control levels after 24 h. This is the first report of PKC δ-mRNA upregulation by TPA which was previously only shown for PKCβ. In view of the antimitogenic actions of PKC δ this pattern of regulation may serve to preserve growth control even in the presence of chronic cell activation