Ascorbate mitigates oxidative stress and hemin cytotoxicity in heme oxygenase-1 deficiency.

ABSTRACT: Heme oxygenase-1 (HO-1) deficiency manifests with severe metabolic abnormalities, yet the underlying mechanisms remain incompletely understood. We investigated metabolic adaptations in HO-1-deficient cells using patient-derived lymphoblastoid cells (LCL) and HEK293T knockout cells. Both cell types exhibited concordant metabolic signatures, characterized by a substantial reduction in intracellular ascorbic acid levels, despite compensatory upregulation of sodium-dependent vitamin C transporter 2 (SVCT2) and downregulation of GLUT1, compared to wild-type cells. Ultrastructural examination revealed abnormal mitochondrial morphology in both models. Both cell types showed higher baseline hydrogen peroxide levels compared to wild-type cells. Treatment with 2-phospho-L-ascorbic acid (AA2P) restor

SUBMITTER: Berendes LS 

PROVIDER: S-EPMC12605015 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature