Glutathione-S-transferase P promotes glycolysis in asthma in association with oxidation of pyruvate kinase M2.

ABSTRACT:

Background

Interleukin-1-dependent increases in glycolysis promote allergic airways disease in mice and disruption of pyruvate kinase M2 (PKM2) activity is critical herein. Glutathione-S-transferase P (GSTP) has been implicated in asthma pathogenesis and regulates the oxidation state of proteins via S-glutathionylation. We addressed whether GSTP-dependent S-glutathionylation promotes allergic airways disease by promoting glycolytic reprogramming and whether it involves the disruption of PKM2.

Methods

We used house dust mite (HDM) or interleukin-1β in C57BL6/NJ WT or mice that lack GSTP. Airway basal cells were stimulated with interleukin-1β and the selective GSTP inhibitor, TLK199. GSTP and PKM2 were evaluated in sputum samples of asthmatics and healthy controls and incorpor

SUBMITTER: van de Wetering C 

PROVIDER: S-EPMC8502950 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature