Phenylbutyric Acid Modulates Apoptosis and ER Stress-Related Gene Expression in Glycogen Storage Disease Type Ib In Vitro Model.

ABSTRACT:

Introduction

Chronic endoplasmic reticulum (ER) stress and increased apoptosis are involved in the pathogenesis of glycogen storage disease Ib (GSD Ib), whereas small molecule phenylbutyrate (4-PBA) showed the capability of reducing ER stress-induced apoptosis. The objective was to generate an in vitro system in which capability of small molecules (SMs) to influence ER stress and apoptosis could be screened at the expression level.

Methods

G6PT-deficient FlpInHEK293 cell line was created and validated using the CRISPR/Cas9 knockout method. Molecular markers of unfolded protein response (ATF4, DDIT3, HSPA5, XBP1s), and apoptosis (BCL2/BAX, CASP3, CASP7) in G6PT-deficient cells were analyzed using RT-qPCR method before and upon the treatment with 4-PBA.

Results

Treatmen

SUBMITTER: Parezanovic M 

PROVIDER: S-EPMC11726116 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature