alexa Apoptosis and Differentiation of K562 Cells by Targeting GST-O1 to Inhibit 4-HNE Metabolism

OMICS International organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Apoptosis and Differentiation of K562 Cells by Targeting GST-O1 to Inhibit 4-HNE Metabolism

Bcr-Abl kinase inhibitors are very effective drugs for treatment of chronic myelogenous leukemia (CML), but treatment options are limited and relatively ineffective for patients with de-novo or acquired resistance. The K562 human erythroleukemia cell line, derived from a pleural effusion during blast crisis of a CML patient, is very useful for studying hematopoietic differentiation because it undergoes differentiation and apoptosis in response to chemicals that propagate lipid-peroxidation. 4-hydroxynonenal (4-HNE), a reactive aldehyde produced from peroxidation of polyunsaturated fatty acids, is metabolized primarily by glutathione S-transferases (GSTs). 4-HNE causes differentiation, apoptosis and necrosis in K562 cells, but cannot be used as a drug for resistant CML because of its highly toxic nature. Present studies addressed the possibility of developing an alternative targeted treatment aimed at increasing intracellular 4-HNE through inhibition of GST. Because the major GST-isoenzymes in leukemia cells are also present in normal tissues, we explored the possibility of modulating cellular 4-HNE levels by inhibiting GST isozymes with high activity towards 4-HNE. Our studies identified the presence of the GSTO1 isoenzyme in K562 cells, demonstrated its activity towards 4-HNE, and showed that its depletion causes apoptosis, necrosis and differentiation of these cells. These effects of GSTO1 depletion appear to involve RUNX1 mediated transcriptional regulation of GM-CSF. These findings offer a new target for treatment of resistant CML.

 

Citation: Leake K, Singhal J, Singhal SS, Awasthi S (2014) Apoptosis and Differentiation of K562 Cells by Targeting GST-O1 to Inhibit 4-HNE Metabolism. Biochem Pharmacol 3:144. doi: 10.4172/2167-0501.1000144

 
  • Share this page
  • Facebook
  • Twitter
  • LinkedIn
  • Google+
  • Pinterest
  • Blogger
 
adwords