			Home About us Contact

Regulating Apoptosis (regulating + apoptosi)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Susceptibility to experimental biliary atresia linked to different hepatic gene expression profiles in two mouse strains

HEPATOLOGY RESEARCH, Issue 2 2010
Johannes Leonhardt
Aim:, To compare hepatic gene expression during the development of experimental biliary atresia (BA) in two different mouse strains. Methods:, Balb/c mice and C57Black/6 (Black/6) mice were infected with rhesus rotavirus (RRV) postpartum, clinical signs of BA and survival were noted. Liver sections were assessed for cluster of differentiation antigen (CD) 3, CD4 and CD8 expression, and the hepatic virus load was determined. Second, mice of both strains were sacrificed three days after infection. Isolated hepatic RNA was subjected to gene expression analysis using Affymetrix Gene Chip MOE 430 2.0. Results:, The incidence of BA was significantly lower in Black/6 mice compared to Balb/c mice (13.5% vs. 67%, P < 0.05). The mean virus titers were higher in mice with BA compared to mice without BA. Different gene profiles three days after virus infection were noted, with differential expression of 201 genes, including those regulating apoptosis, nucleic acid binding, transport function and particularly the immune response (chemokine C-C motif ligand 2, toll-like receptor 3, CD antigen 14, chemokine (C-X-C motif) ligands 10 and 11). This correlated with a significant increase of CD4 positive cells only in Balb/c mice with BA compared to healthy mice (13.5 vs. 5.0; P < 0.05). Black/6 mice did not exhibit any significant increase of CD3 or CD4 leukocytes despite cholestasis. Conclusion:, The different susceptibility to experimental BA was associated with an increase of CD4 T-cells in the liver of Balb/c mice, which is linked to different gene profiles at the onset of bile duct obstruction. [source]

A hierarchical analysis of transcriptome alterations in intrauterine growth restriction (IUGR) reveals common pathophysiological pathways in mammals,

THE JOURNAL OF PATHOLOGY, Issue 3 2007
C Buffat
Abstract Intra-uterine growth restriction (IUGR) is a frequent disease, affecting up to 10% of human pregnancies and responsible for increased perinatal morbidity and mortality. Moreover, low birth weight is an important cause of the metabolic syndrome in the adult. Protein depletion during the gestation of rat females has been widely used as a model for human IUGR. By transcriptome analysis of control and protein-deprived rat placentas, we were able to identify 2543 transcripts modified more than 2.5 fold (1347 induced and 1196 repressed). Automatic functional classification enabled us to identify clusters of induced genes affecting chromosome structure, transcription, intracellular transport, protein modifications and apoptosis. In particular, we suggest the existence of a complex balance regulating apoptosis. Among repressed genes, we noted several groups of genes involved in immunity, signalling and degradation of noxious chemicals. These observations suggest that IUGR placentas have a decreased resistance to external aggression. The promoters of the most induced and most repressed genes were contrasted for their composition in putative transcription factor binding sites. There was an over-representation of Znfinger (ZNF) proteins and Pdx1 (pancreatic and duodenal homeobox protein 1) putative binding sites. Consistently, Pdx1 and a high proportion of ZNF genes were induced at the transcriptional level. A similar analysis of ZNF promoters showed an increased presence of putative binding sites for the Tata box binding protein (Tbp). Consistently again, we showed that the Tbp and TBP-associated factors (Tafs) were up-regulated in IUGR placentas. Also, samples of human IUGR and control placentas showed that human orthologous ZNFs and PDX1 were transcriptionnally induced, especially in non-vascular IUGR. Immunohistochemistry revealed increased expression of PDX1 in IUGR human placentas. In conclusion, our approach permitted the proposition of hypotheses on a hierarchy of gene inductions/repressions leading to massive transcriptional alterations in the IUGR placenta, in humans and in rodents. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Association of p53 polymorphism with ICSI/IVF failure and recurrent pregnancy loss

AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2009
FIROUZABADI Razieh Dehghani
Background: The p53 tumour suppressor gene is a well-known factor regulating apoptosis in a wide variety of cells. Alterations in the p53 gene are among the most common genetic changes in human cancers. Several polymorphisms of the p53 tumour suppressor gene have been associated with recurrent pregnancy loss (RPL). Aims: To evaluate the association of polymorphisms p53 codon 72 with the response to in vitro fertilisation (IVF) treatment and occurrence of repeated miscarriages. Methods: The homozygous and heterozygous genotypes and allelic frequencies of Arg and Pro p53 at codon 72 were identified by using polymerase chain reaction,restriction fragment length polymorphism technique in 70 infertile women with more than two IVF failures. Each comparison was made with 97 women experiencing RPL and 32 fertile women each with at least two healthy children as the control group. Results: The frequency of homozygous Pro/Pro genotypes was found significantly higher among the women with RPL than the other two groups (P = 0.041). Whereas, Arg/Arg genotype was significantly different in the recurrent implantation failure (RIF) group (P = 0.005). Conclusion: It is concluded that p53 codon 72 polymorphism may serve as a susceptible factor affecting the chances of RPL and RIF. [source]

Baculovirus P35 protein: An overview of its applications across multiple therapeutic and biotechnological arenas

BIOTECHNOLOGY PROGRESS, Issue 2 2010
Sudhir Sahdev
Abstract Baculovirus immediate early P35 protein is well known for its anti-apoptotic as well as anti-oxidant properties. Mechanism of action of P35 involves inhibition of a vast range of initiator to executioner class of caspases. In addition, P35's role in inhibiting oxidant-induced mitochondrial damage, primarily in the apoptotic pathway, has also been extensively investigated. Elucidation of P35's functions during regulation of programmed cell death (PCD) has led to a renewed focus on exploiting this basic knowledge for clinical and other related applications. This review outlines specific biochemical and genetic pathways where P35 intervenes and regulates rate-limiting steps in the apoptotic signaling cascade. Research efforts are underway to utilize P35 as an agent in regulating apoptosis and under certain circumstances, also explore the therapeutic potential of its anti-oxidant features. One of the major outcomes of recent studies include significantly improved effectiveness of cytochrome P450 directed enzyme pro-drug delivery tools when used in conjunction with P35, which may help in alleviating drug resistance in tumor cells and simultaneously prolonging the cytotoxic effects of anti-cancer drugs. Moreover, applied research carried out recently in the fields of diabetes, ischemia-induced neuronal cell death, experimental autoimmune encephalomyelitis (EAE), multiple sclerosis (MS), inflammatory arthritis, cardiovascular and ocular disorders illustrate P35's utilization across diverse therapeutic areas and will certainly make it an attractive biomolecule for the discovery research. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010 [source]