MiPsummer Programme pdf - Mitochondrial Physiology Society

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Abstract # 38
Evidence that fibroblasts from patients affected by Medium-Chain Acyl-Coa Dehydrogenase
Deficiency (MCADD) are under chronic oxidative stress
A. M. Tonin 1,2 , P. Fernandez-Guerra 1 , N. Cornelius 1 , R. K. J. Olsen 1 , M. Wajner 2 and N.
Gregersen 1
1 Research Unit for Molecular Medicine, Department of Clinical Medicine, Health, Aarhus
University and Aarhus University Hospital, Skejby, Aarhus, Denmark
2 Federal University of Rio Grande do Sul, Porto Alegre, Brazil
Background Mutations in the ACADM gene causes MCADD. The clinical features are variable and
the physiopathology has been related to energy deficiency, accumulation of toxic metabolites and
presence or lack of misfolded MCAD protein, resulting in oxidative stress.
Objectives To evaluate the extent of mitochondrial oxidative stress under different metabolic
conditions in cultured skin fibroblasts of controls and MCADD patients carrying distinct ACADM
mutations.
Results Fibroblasts were grown in standard glucose concentration (11mmol/L) and after 24hrs the
media were replaced by galactose (11mmol/L) or galactose and palmitate (100µmol/L). At
standard glucose concentration, patient fibroblasts presented higher levels of mitochondrial
superoxide compared to controls fibroblasts. In galactose media, the percentage of stressed cells in
all groups increased, but the level of superoxide was still higher in the patient fibroblasts. When
galactose plus palmitate media was used, patient fibroblasts with the c.[199TC] + [985AG]
genotype, associated with mild disease, seem to have higher superoxide levels than patients
carrying null mutations.
Conclusion These results indicate that fibroblasts of MCADD patients are under chronic oxidative
stress. It could be speculated that such mild stress exposure could induce an adaptive response,
protecting cells against oxidative damage during pathological situations of metabolic stress like
feverish infections.