Oxidative stress is believed to be an important mediator of neurodegeneration. However, the transcriptional pathways induced in neurons by oxidative stress that activate protective gene responses have yet to be fully delineated. We report that the transcription factor Sp1 is acetylated in response to oxidative stress in neurons. Histone deacetylase (HDAC) inhibitors augment Sp1 acetylation, Sp1 DNA binding, and Sp1-dependent gene expression and confer resistance to oxidative stress-induced death in vitro and in vivo . Sp1 activation is necessary for the protective effects of HDAC inhibitors. Together, these results demonstrate that HDAC inhibitors inhibit oxidative death independent of polyglutamine expansions by activating an Sp1-dependent adaptive response.
A trend toward a higher incidence of hepatocelullar carcinoma (HCC) in patients with cirrhosis treated with bare-stent transjugular intrahepatic portosystemic shunt (TIPS) has been observed in previous studies. To assess the influence of TIPS as a risk factor for developing HCC, we have compared the incidence of HCC in two retrospective cohorts of patients. The TIPS cohort (n ؍ 138) included patients with cirrhosis who underwent TIPS placement for the treatment of portal hypertension-related complications; the non-TIPS cohort was composed of patients admitted at the hospital at the same time of TIPS insertion who were individually H epatocellular carcinoma (HCC) is a wellknown complication of cirrhosis. The incidence of this neoplasm has increased worldwide in the last few decades, 1-4 and it currently represents one of the major causes of death in patients with end-stage liver disease. 5 Cirrhosis is considered the major risk factor for developing HCC. 6 Male sex, older age, advanced ChildTurcotte-Pugh class, and viral and alcoholic causes of cirrhosis have been consistently associated with HCC in different studies. 5,7 Other risk factors for developing HCC, however, are not as well defined, due in part to the difficulty of performing epidemiological studies on this condition.Transjugular intrahepatic portosystemic shunt (TIPS) is an invasive procedure in which a side-to-side portacaval shunt is created by placing a stent between the portal vein and a hepatic vein or the cava vein. Because this procedure effectively reduces portal pressure, it is widely used to treat portal hypertensionrelated complications. [8][9][10] A potential association between surgical portosystemic shunting and the development of HCC has been suggested in a retrospective study of autopsies performed on patients who had cirrhosis, 11 but this association has not been confirmed by other studies. 12 Although TIPS is not a surgical shunt, it generates similar circulatory, hemodynamic, and functional changes. As in surgical shunts, two recent preliminary studies have observed higher 13 and unchanged 14 incidence of HCC in patients with noncovered TIPS. Clearly more controlled observations with longer follow-up are needed to better assess the influence of TIPS on the development of HCC. Therefore, we designed a clinical retrospective cohort study to evaluate TIPS as a risk factor for developing HCC. From the
The phosphotriesterase in chicken serum that hydrolyses O-hexyl O-2,5-dichlorophenyl phosphoramidate (HDCP) was purified in three chromatographic steps. The activity copurified to apparent homogeneity with albumin monitoring by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS/ PAGE) and by SDS-capillary electrophoresis in the purified fractions. Commercial chicken serum albumin was further purified and the phosphotriesterase activity remained associated with albumin. Capillary electrophoresis established a molecular weight of 59 +/- 4 kDa for both purified proteins (chicken serum and commercial chicken serum albumin). The purified samples were assayed for hydrolytic activity against several carboxylesters, organophosphates and phosphoramidates. From carboxylesters, only p-nitrophenylbutyrate (p-NPB) hydrolysing activity was found to copurify with the phosphotriesterase. The purified human, chicken, rabbit and bovine serum albumins and recombinant human serum albumin obtained from commercial sources hydrolysed HDCP and p-NPB. Serum albumin also hydrolysed O-butyl O-2,5-dichlorophenyl phosphoramidate, O-ethyl O-2,5-dichlorophenyl phosphoramidate and O-2,5-dichlorophenyl ethylphosphonoamidate but not other organophosphates and phosphoramidates.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.