Sulfite oxidase is a mitochondria-located molybdenum-containing enzyme catalyzing the oxidation of sulfite to sulfate in the amino acid and lipid metabolism. Therefore, it plays a major role in detoxification processes, where defects in the enzyme cause a severe infant disease leading to early death with no efficient or cost-effective therapy in sight. Here we report that molybdenum trioxide (MoO3) nanoparticles display an intrinsic biomimetic sulfite oxidase activity under physiological conditions, and, functionalized with a customized bifunctional ligand containing dopamine as anchor group and triphenylphosphonium ion as targeting agent, they selectively target the mitochondria while being highly dispersible in aqueous solutions. Chemically induced sulfite oxidase knockdown cells treated with MoO3 nanoparticles recovered their sulfite oxidase activity in vitro, which makes MoO3 nanoparticles a potential therapeutic for sulfite oxidase deficiency and opens new avenues for cost-effective therapies for gene-induced deficiencies.
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http://dx.doi.org/10.1021/nn501235j | DOI Listing |
Cytotechnology
February 2025
Department of Physiology, Faculty of Medicine, Pamukkale University, Denizli, Türkiye.
S-Sulfocysteine (SSC) is a metabolite derived from the metabolism of sulfur-containing amino acids. It has been implicated in neurotoxicity observed in children with sulfite oxidase deficiency. The aim of our study was to confirm the neurotoxic effects of SSC using a mouse hippocampal cell line (HT-22) and to investigate the role of apoptosis in these effects, especially in terms of caspase-3 activation and genotoxicity.
View Article and Find Full Text PDFPharmacol Ther
February 2025
Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address:
Hydrogen sulfide (HS) is an environmental hazard well known for its neurotoxicity. In mammalian cells, HS is predominantly generated by transsulfuration pathway enzymes. In addition, HS produced by gut microbiome significantly contributes to the total sulfide burden in the body.
View Article and Find Full Text PDFMetab Brain Dis
December 2024
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, 90035-003, RS, Brazil.
Sulfite oxidase deficiencies, either caused by deficiency of the apoenzyme or the molybdenum cofactor, and ethylmalonic encephalopathy are inherited disorders that impact sulfur metabolism. These patients present with severe neurodeterioration accompanied by cerebral cortex and cerebellum abnormalities, and high thiosulfate levels in plasma and tissues, including the brain. We aimed to clarify the mechanisms of such abnormalities, so we assessed the ex vivo effects of thiosulfate administration on energetic status and oxidative stress markers in cortical and cerebellar tissues of newborn rats.
View Article and Find Full Text PDFCan J Neurol Sci
December 2024
Child Neurology and Psychiatry Unit, Pediatric Neurophysiology Laboratory, Mother-Child Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
Genet Med Open
May 2024
Department of Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
Purpose: Molybdenum cofactor deficiency (MoCD) classically presents shortly after birth, with neurological symptoms ascribed to postnatal toxicity of accumulating sulphite. Case reports suggest that cerebral damage associated with MoCD may have a prenatal onset.
Methods: A meta-analysis of case reports was performed on individuals with genetically proven MoCD retrieved through a systematic review and in-house search.
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