{"id":119,"date":"2017-11-09T11:52:49","date_gmt":"2017-11-09T02:52:49","guid":{"rendered":"http:\/\/www.neuroscienceres.com\/?p=119"},"modified":"2022-01-07T10:02:55","modified_gmt":"2022-01-07T03:02:55","slug":"binding-ing1-p53-reported-required-activity-prevent","status":"publish","type":"post","link":"http:\/\/www.neuroscienceres.com\/index.php\/2017\/11\/09\/binding-ing1-p53-reported-required-activity-prevent\/","title":{"rendered":"Binding of ING1 to p53 was reported to be required for activity and may prevent"},"content":{"rendered":"

The cytokine is over-expressed in adipose<\/a> tissue of different models of obesity and known to inhibit insulin signalling. Moreover, immuno-neutralization of TNFa in Zucker fa\/fa rats has been shown to increase insulin receptor autophosphorylation and phosphorylation of insulin receptor substrate- 1 in muscle and adipose tissue and to reduce glucose, insulin and FFA plasma levels. In our study, we now demonstrate, for the first time, a very strong increase in TNFa expression in pancreatic b-cells from fa\/fa rats. That such an increase could interfere in b-cell function cannot be excluded; its importance should nevertheless be dampened by the drastic decrease in TNFR2 receptor expression and its delocalization; the receptor seems much less co-localized with insulin granules. The increased expression of TNFa could however be partly responsible for the marked increase in IL-6 expression we found in pancreatic b-cells; indeed, TNFa has been reported to up-regulate IL-6 in murine pancreatic islets. No consistent in vitro data are available regarding insulin secretion in human and rodent islets. However, the marked increase in IL-6 expression together with a clear delocalization to insulin granules questions the possible involvement of IL-6 in the hyperinsulinemia of fa\/fa rats, which deserves to be reassessed in vivo in this model of prediabetic state. Concerning b-cell survival, IL-6 has been shown to stimulate human islet cell proliferation and to afford protection against IL-1b, TNFa and IFNc-induced cell death. Such an effect could occur in pancreatic islets and account for the marked decrease in active caspase-3 expression; indeed, chronic exposure of neurons to IL-6 prevents the enhancement of the cleaved caspase-3 levels induced by NMDA. Finally, from our abArray study, it appears that up- and down regulation of Vorinostat HDAC inhibitor<\/a> factors involved in the regulation of cell proliferation\/ survival, Perifosine clinical trial<\/a> contributes to control islet hyperplasia known to occur in fa\/fa rats. We may conclude that pancreatic islets from hyperphagic, obese insulin-resistant Zucker fa\/fa rats undergo a clear and possibly selfperpetuating inflammatory process. The complexity of cytokines effects and of their interactions makes it difficult to evaluate their pathogenic role in b-cell hyperactivity that compensates for insulin resistance. In Zucker rats, compensation will keep going, but in the presence of an additional b-cell defect, as in ZDF rats, inflammation will be exacerbated and diabetes will ensue. Prion diseases, known as transmissible spongiform encephalopathies , are fatal progressive neurodegenerative diseases characterized with spongiosis and neuronal loss in the central nervous system. PrP is a glycosylphosphatidylinositol -anchored membrane protein expressed mainly in CNS, whose normal function is still enigmatic.<\/p>\n","protected":false},"excerpt":{"rendered":"

The cytokine is over-expressed in adipose tissue of different models of obesity and known to inhibit insulin signalling. Moreover, immuno-neutralization of TNFa in Zucker fa\/fa rats has been shown to increase insulin receptor autophosphorylation and phosphorylation of insulin receptor substrate- 1 in muscle and adipose tissue and to reduce glucose, insulin and FFA plasma levels. … Continue reading Binding of ING1 to p53 was reported to be required for activity and may prevent<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1],"tags":[],"_links":{"self":[{"href":"http:\/\/www.neuroscienceres.com\/index.php\/wp-json\/wp\/v2\/posts\/119"}],"collection":[{"href":"http:\/\/www.neuroscienceres.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/www.neuroscienceres.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/www.neuroscienceres.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/www.neuroscienceres.com\/index.php\/wp-json\/wp\/v2\/comments?post=119"}],"version-history":[{"count":1,"href":"http:\/\/www.neuroscienceres.com\/index.php\/wp-json\/wp\/v2\/posts\/119\/revisions"}],"predecessor-version":[{"id":120,"href":"http:\/\/www.neuroscienceres.com\/index.php\/wp-json\/wp\/v2\/posts\/119\/revisions\/120"}],"wp:attachment":[{"href":"http:\/\/www.neuroscienceres.com\/index.php\/wp-json\/wp\/v2\/media?parent=119"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/www.neuroscienceres.com\/index.php\/wp-json\/wp\/v2\/categories?post=119"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/www.neuroscienceres.com\/index.php\/wp-json\/wp\/v2\/tags?post=119"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}