biostudies-literatureSantoro AMinistry of University and ResearchMinistry of University and Research, Progetti di Ricerca Nazionale (PRIN)Italian Ministry of Education, Universities, and Research (MIUR)Italian Ministry of Education, Universities, and ResearchU.S. National Cancer Institute13314https://www.ebi.ac.uk/biostudies/studies/S-EPMC11679772biostudies-literatureUnknown25(24)Mutations in the SLC25A38 gene are responsible for the second most common form of congenital sideroblastic anemia (CSA), a severe condition for which no effective treatment exists. We developed and characterized a K562 erythroleukemia cell line with markedly reduced expression of the SLC25A38 protein (A38-low cells). This model successfully recapitulated the main features of CSA, including reduced heme content and mitochondrial respiration, increase in mitochondrial iron, ROS levels and sensitivity to oxidative stress. Notably, our study uncovered a new role for extracellular pyridoxal 5'-phosphate (PLP) and other P2 receptor antagonists in rescuing the altered parameters of A38-low cells (for example, the heme content of the A38-low cells was increased from about 50% to about 80% by the PInternational journal of molecular sciencesP2 Receptor Antagonists Rescue Defective Heme Content in an In Vitro SLC25A38-Associated Congenital Sideroblastic Anemia Cell Model.PMC11679772B73C220012500062017PAB8EM_005CA2178092017PAB8EM_005 "Membrane transporters, the doors of cellular metabolism. Investigations of biochemical features structure/function relationships, metabolic regulation and physiopathological aspects by in vitro and in vivo experimental models" to E.P.;RBSI14LTISRBSI14LTIS "Molecular and pathogenetic mechanism of congenital sideroblastic anemia associated with the SLC25A38 gene deficiency" to E.P.CA217809 to E.T.K.Marobbio CMTKool ETPalazzo AParadies EPalmieri LSantoro ARusso RAgrimi GPalmieri FJun YWIolascon AFiermonte GVozza AAndolfo IStorlazzi CTFerrucci ADe Santis SfalseP2 Receptor Antagonists Rescue Defective Heme Content in an In Vitro SLC25A38-Associated Congenital Sideroblastic Anemia Cell Model.Mutations in the SLC25A38 gene are responsible for the second most common form of congenital sideroblastic anemia (CSA), a severe condition for which no effective treatment exists. We developed and characterized a K562 erythroleukemia cell line with markedly reduced expression of the SLC25A38 protein (A38-low cells). This model successfully recapitulated the main features of CSA, including reduced heme content and mitochondrial respiration, increase in mitochondrial iron, ROS levels and sensitivity to oxidative stress. Notably, our study uncovered a new role for extracellular pyridoxal 5'-phosphate (PLP) and other P2 receptor antagonists in rescuing the altered parameters of A38-low cells (for example, the heme content of the A38-low cells was increased from about 50% to about 80% by the P2024-01-01T00:00:00Z2024 Dec2026-05-22T03:11:41.126Z2026-05-22T03:08:00.708ZS-EPMC116797723976908710.3390/ijms252413314