Displacement of Native FXYD Protein From Na⁺/K⁺-ATPase With Novel FXYD Peptide Derivatives: Effects on Doxorubicin Cytotoxicity.

ABSTRACT: The seven mammalian FXYD proteins associate closely with α/β heterodimers of Na⁺/K⁺-ATPase. Most of them protect the β1 subunit against glutathionylation, an oxidative modification that destabilizes the heterodimer and inhibits Na⁺/K⁺-ATPase activity. A specific cysteine (Cys) residue of FXYD proteins is critical for such protection. One of the FXYD proteins, FXYD3, confers treatment resistance when overexpressed in cancer cells. We developed two FXYD3 peptide derivatives. FXYD3-pep CKCK retained the Cys residue that can undergo glutathionylation and that is critical for protecting the β1 subunit against glutathionylation. FXYD3-pep SKSK had all Cys residues mutated to Serine (Ser). The chemotherapeutic doxorubicin induces oxidative stress, and s

SUBMITTER: Liu CC 

PROVIDER: S-EPMC8968713 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature