Resveratrol-induced cytotoxicity in human Burkitt's lymphoma cells is coupled to the unfolded protein response

<p>Abstract</p> <p>Background</p> <p>Resveratrol (RES), a natural phytoalexin found at high levels in grapes and red wine, has been shown to induce anti-proliferation and apoptosis of human cancer cell lines. However, the underlying molecular mechanisms are at present only partially understood.</p> <p>Method</p> <p>The effects of RES on activation of unfolded protein responses (UPR) were evaluated using Western blotting, semi-quantitative and real-time RT-PCR. Cell death was evaluated using Annexin V/PI staining and subsequent FACS.</p> <p>Results</p> <p>Similar as tunicamycin, treatment with RES lead to the activation of all 3 branches of the UPR, with early splicing of XBP-1 indicative of IRE1 activation, phosphorylation of eIF2α consistent with ER resident kinase (PERK) activation, activating transcription factor 6 (ATF6) splicing, and increase in expression levels of the downstream molecules GRP78/BiP, GRP94 and CHOP/GADD153 in human Burkitt's lymphoma Raji and Daudi cell lines. RES was shown to induce cell death, which could be attenuated by thwarting upregulation of CHOP.</p> <p>Conclusions</p> <p>Our data suggest that activation of the apoptotic arm of the UPR and its downstream effector CHOP/GADD153 is involved, at least in part, in RES-induced apoptosis in Burkitt's lymphoma cells.</p

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Mulheres da segurança pública do litoral do Paraná, Brasil: intersecções entre gênero, trabalho, violência(s) e saúde

This study aimed to promote visibility of women working in public security along the Parana coast, articulating issues of gender, violence(s), and the health-disease process. The methodology was qualitative, through an ethnographic research which included 50 women (civilians, military policewomen, and prison officers) from municipalities along the Parana coast, between March 2014 and March 2015. Results revealed: 1) the dilemmas that these women are subjected to, facing the seasonal dynamics in the field of public security in the region2) exposure to violence (mainly institutional and gender-based) and its impact on these women's health3) power relations, marked by corporations' hierarchies and gender asymmetries between men and women in professional settings. In summary, this research highlighted the need to promote visibility of women working in public security institutions, considering the impact of violence and gender inequalities in their personal and professional lives, including the resistance and rearrangements promoted by these women in the institutions in response to their presence in a hegemonic and traditionally male environment.Este artigo busca compreender as relações entre gênero, violências e o processo saúde-doença de mulheres que trabalham na área de segurança pública no litoral do estado do Paraná. A metodologia foi qualitativa, por meio de pesquisa etnográfica com 50 mulheres (policiais civis e militares, e agentes penitenciárias), realizada em três municípios balneários da região entre março de 2014 e março de 2015. A análise dos resultados revelou: 1) dilemas concernentes às sobrecargas de trabalho impostas pela conjuntura local, marcada pela sazonalidade; 2) exposição às violências (principalmente institucional e de gênero) e repercussão na saúde dessas mulheres; 3) relações de poder, assinaladas pelas hierarquias das corporações e assimetrias de gênero entre profissionais homens e mulheres. Esta pesquisa evidenciou: como as profissionais femininas nas instituições de segurança pública sofrem diretamente o impacto das violências e desigualdades de gênero em suas vidas pessoais e profissionais; e as resistências e rearranjos dessas mulheres nas instituições, suas reinvenções em meio a um ambiente de hegemonia tradicionalmente masculina.Univ Fed Parana UFPR, Programa Posgrad Desenvolvimento Terr Sustentavel, R 15 Novembro 1299, BR-80060000 Curitiba, Parana, BrazilUFPR, Camara Saude Colet, Curitiba, Parana, BrazilUniv Fed São Paulo, Escola Paulista Med, São Paulo, SP, BrazilUniv Fed São Paulo, Escola Paulista Med, São Paulo, SP, BrazilWeb of Scienc