Dramatic elevation in urinary amino terminal titin fragment excretion quantified by immunoassay in Duchenne muscular dystrophy patients and in dystrophin deficient rodents

Autor: Janet DiPiero, Glen B. Banks, Leslie K. Jacobsen, Nino Devidze, Denise Bounous, Linda J. Bristow, Stephen A. Stimpson, Sean C. Little, Michael K. Ahlijanian, Robert C. Gagnon, Courtney M. Smith, Mark J. Majchrzak, Alan S. Robertson, Fizal Nabbie
Rok vydání: 2017
Předmět:
0301 basic medicine
medicine.medical_specialty
mdx mouse
Adolescent
Duchenne muscular dystrophy
Immunoenzyme Techniques
03 medical and health sciences
Mice
0302 clinical medicine
Adrenal Cortex Hormones
Internal medicine
Troponin I
Medicine
Animals
Humans
Connectin
Muscular dystrophy
Child
Creatine Kinase
Genetics (clinical)
biology
business.industry
Age Factors
food and beverages
Skeletal muscle
Muscular Dystrophy
Animal
musculoskeletal system
medicine.disease
Muscular Dystrophy
Duchenne
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Cross-Sectional Studies
Neurology
Case-Control Studies
Child
Preschool
Pediatrics
Perinatology and Child Health
cardiovascular system
biology.protein
Mice
Inbred mdx
Titin
Creatine kinase
Neurology (clinical)
business
Dystrophin
tissues
human activities
030217 neurology & neurosurgery
Zdroj: Neuromuscular disorders : NMD. 27(7)
ISSN: 1873-2364
Popis: Enzyme-linked and electrochemiluminescence immunoassays were developed for quantification of amino (N-) terminal fragments of the skeletal muscle protein titin (N-ter titin) and qualified for use in detection of urinary N-ter titin excretion. Urine from normal subjects contained a small but measurable level of N-ter titin (1.0 ± 0.4 ng/ml). A 365-fold increase (365.4 ± 65.0, P = 0.0001) in urinary N-ter titin excretion was seen in Duchene muscular dystrophy (DMD) patients. Urinary N-ter titin was also evaluated in dystrophin deficient rodent models. Mdx mice exhibited low urinary N-ter titin levels at 2 weeks of age followed by a robust and sustained elevation starting at 3 weeks of age, coincident with the development of systemic skeletal muscle damage in this model; fold elevation could not be determined because urinary N-ter titin was not detected in age-matched wild type mice. Levels of serum creatine kinase and serum skeletal muscle troponin I (TnI) were also low at 2 weeks, elevated at later time points and were significantly correlated with urinary N-ter titin excretion in mdx mice. Corticosteroid treatment of mdx mice resulted in improved exercise performance and lowering of both urinary N-ter titin and serum skeletal muscle TnI concentrations. Low urinary N-ter titin levels were detected in wild type rats (3.0 ± 0.6 ng/ml), while Dmdmdx rats exhibited a 556-fold increase (1652.5 ± 405.7 ng/ml, P = 0.002) (both at 5 months of age). These results suggest that urinary N-ter titin is present at low basal concentrations in normal urine and increases dramatically coincident with muscle damage produced by dystrophin deficiency. Urinary N-ter titin has potential as a facile, non-invasive and translational biomarker for DMD.
Databáze: OpenAIRE
Externí odkaz: