Phosphocyclocreatine is the dominant form of cyclocreatine in control and creatine transporter deficiency patient fibroblasts

Autor: Elizabeth A. Ottinger, Minh-Ha Do, Marc Singleton, Bradley Class, Kirill Gorshkov, Ethan G. Fisher, Nicola Longo, Wei Zheng, Wenwei Huang, Xin Xu, Wei Sun, Amy Wang, Natasha Thorne, Marta Frigeni
Rok vydání: 2019
Předmět:
creatine transporter deficiency
cyclocreatine
Primary Cell Culture
RM1-950
Pharmacology
Imidazolidines
Creatine
Plasma Membrane Neurotransmitter Transport Proteins
environment and public health
030226 pharmacology & pharmacy
Phosphocreatine
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Tandem Mass Spectrometry
medicine
Humans
General Pharmacology
Toxicology and Pharmaceutics
Cells
Cultured
Chromatography
High Pressure Liquid
phosphocreatine
integumentary system
Chemistry
fungi
Metabolic disorder
Brain Diseases
Metabolic
Inborn
HILIC UPLC–MS/MS method
Fibroblasts
medicine.disease
creatine
Neurology
Creatinine
030220 oncology & carcinogenesis
Creatine transporter deficiency
Mental Retardation
X-Linked
phosphocyclocreatine
Phosphorylation
Original Article
Therapeutics. Pharmacology
CTD
Early Career Researcher Themed Issue
Phosphocyclocreatine
Intracellular
Zdroj: Pharmacology Research & Perspectives, Vol 7, Iss 6, Pp n/a-n/a (2019)
Pharmacology Research & Perspectives
ISSN: 2052-1707
DOI: 10.1002/prp2.525
Popis: Creatine transporter deficiency (CTD) is a metabolic disorder resulting in cognitive, motor, and behavioral deficits. Cyclocreatine (cCr), a creatine analog, has been explored as a therapeutic strategy for the treatment of CTD. We developed a rapid, selective, and accurate HILIC ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) method to simultaneously quantify the intracellular concentrations of cCr, creatine (Cr), creatine‐d3 (Cr‐d3), phosphocyclocreatine (pcCr), and phosphocreatine (pCr). Using HILIC‐UPLC‐MS/MS, we measured cCr and Cr‐d3 uptake and their conversion to the phosphorylated forms in primary human control and CTD fibroblasts. Altogether, the data demonstrate that cCr enters cells and its dominant intracellular form is pcCr in both control and CTD patient cells. Therefore, cCr may replace creatine as a therapeutic strategy for the treatment of CTD.
Databáze: OpenAIRE
Externí odkaz: