PARP-1 and YY1 Are Important Novel Regulators of CXCL12 Gene Transcription in Rat Pancreatic Beta Cells

Despite significant progress, the molecular mechanisms responsible for pancreatic beta cell depletion and development of diabetes remain poorly defined. At present, there is no preventive measure against diabetes. The positive impact of CXCL12 expression on the pancreatic beta cell prosurvival phenotype initiated this study. Our aim was to provide novel insight into the regulation of rat CXCL12 gene (Cxcl12) transcription. The roles of poly(ADP-ribose) polymerase-1 (PARP-1) and transcription factor Yin Yang 1 (YY1) in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation. The regulatory activities of PARP-1 and YY1 were assessed in transfection experiments using a reporter vector with a Cxcl12 promoter sequence driving luciferase gene expression. Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription. Streptozotocin (STZ)-induced general toxicity in pancreatic beta cells was followed by changes in Cxcl12 promoter regulation. PARP-1 binding to the Cxcl12 promoter during basal and in STZ-compromised conditions led us to conclude that PARP-1 regulates constitutive Cxcl12 expression. During the early stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter while PARP-1 displayed strong binding. These interactions were accompanied by Cxcl12 downregulation. In the later stages of oxidative stress and intensive pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12 promoter in contrast to PARP-1. These interactions resulted in higher Cxcl12 expression. The observed ability of PARP-1 to downregulate, and of YY1 to upregulate Cxcl12 promoter activity anticipates corresponding effects in the natural context where the functional interplay of these proteins could finely balance Cxcl12 transcription

Perfil dos internos no sistema prisional do Rio de Janeiro: especificidades de gênero no processo de exclusão social Profile of prisoners in the Rio de Janeiro prison system: specifities of gender in the social exclusion process

O estudo do perfil sociodemográfico, história penal, uso de drogas e doenças sexualmente transmissíveis da população carcerária do Estado do Rio de Janeiro, em 1998, permitiu conhecer diferentes características da população prisional por sexo. O objetivo deste estudo é identificar se o perfil de exclusão social a que essa população é submetida difere quanto ao sexo. Foram entrevistados 2.039 presos por estudo seccional, e utilizada a razão de prevalência como medida de associação entre sexo e as demais variáveis. A análise multivariada, através de regressão logística, compõe um modelo final de explicação dessas diferenças. A população é jovem, de baixa escolaridade, e apresenta ruptura de vínculos da vida social em várias dimensões para ambos os sexos. Fatores mais fortemente associados ao sexo masculino: visita íntima na prisão, estar preso por sete anos ou mais, ser casado, condenação por roubo, ter ainda três anos ou mais a cumprir de pena e uso de maconha antes de ser preso; para o sexo feminino: doença sexualmente transmissível, ser viúva, estrangeira, usar tranqüilizante na prisão, ter visitado alguém na prisão antes de ser presa e ter 35 anos ou mais. A análise dos dados permitiu concluir que embora esses homens e mulheres sejam igualmente excluídos da "vida social" muito antes e também depois da prisão, existem algumas características que os diferenciam nesse processo de injustiça social.<br>The study of the social and demographic profile, criminal records, drug use and sexually transmitted diseases of the prison population of Rio de Janeiro State in 1998 offered a view of different aspects of this population by gender. The objective of this study is to identify if the profile of social exclusion this population is submitted differs by gender. Through a sectional study, 2,039 prisoners were interviewed, using the prevalence ratio as an association measure between gender and the other variables. Multivariate analysis, using logistical regression, explains these differences in a final model. This population is young and poorly educated, with breakdowns in the links of social life at various levels for both men and women. Factors most strongly associated with men: marital visits in jail, imprisoned for seven years or more, married, sentenced for robbery, have three years or more of the sentence to complete, and having smoked marijuana prior to being arrested; for women: sexually transmitted disease, widowed, non-Brazilian, take tranquilizers in jail, visited someone in jail before being arrested, 35 years old or more. Data analysis permits to conclude that although these men and women are just as excluded from "social life" long before and also after their imprisonment, there are some aspects that make them different in this process of social injustice