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Elevated serum creatine phosphokinase in choline-deficient humans:mechanistic studies in C2C12 mouse myoblasts

Domenii publicaţii > Ştiinţe medicale + Tipuri publicaţii > Articol în revistã ştiinţificã

Autori: Kerry-Ann da Costa, Mihaela Badea, Leslie M Fischer, and Steven H Zeisel

Editorial: American Journal of Clinical Nutrition, 80, p.163–, 2004.

Rezumat:

Background: Choline is a required nutrient, and humans deprived
of choline develop liver damage.
Objective: This study examined the effect of choline deficiency on
muscle cells and the release of creatine phosphokinase (CPK) as a
sequela of that deficiency.
Design: Four men were fed diets containing adequate and deficient
amounts of choline, and serum was collected at intervals for measurement
of CPK. C2C12 mouse myoblasts were cultured in a defined
medium containing 0 or 70 mol choline/L for up to 96 h, and
CPK was measured in the media; choline and metabolites were
measured in cells. Apoptosis was assessed by using terminal deoxynucleotidyl
transferase–mediated dUTP-biotin end labeling and activated
caspase-3 immunohistochemistry. Cell fragility in response
to hypo-osmotic stress was also assessed.
Results: Three of 4 humans fed a choline-deficient diet had significantly
elevated serum CPK activity derived from skeletal muscle
(up to 66-fold; P0.01) that resolved when choline was restored to
their diets. Cells grown in choline-deficient medium for 72 h leaked
3.5-fold more CPK than did cells grown in medium with 70 mol
choline/L (control medium; P  0.01). Apoptosis was induced in
cells grown in choline-deficient medium. Phosphatidylcholine concentrations
were diminished in choline-deficient cells (to 43% of
concentrations in control cells at 72 h; P  0.01), as were concentrations
of intracellular choline, phosphocholine, and glycerophosphocholine.
Cells grown in choline-deficient medium had greater
membrane osmotic fragility than did cells grown in control medium.
Conclusions: Choline deficiency results in diminished concentrations
of membrane phosphatidylcholine in myocytes, which makes
them more fragile and results in increased leakage ofCPKfrom cells.
SerumCPKmay be a useful clinical marker for choline deficiency in
humans.

Cuvinte cheie: creatin fosfokinaza, deficienta colina, muschi, mioblasti, apoptoza, fosfatidilcolina // Creatine phosphokinase, choline deficiency, muscle, myoblasts, apoptosis, phosphatidylcholine