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Abstract Details

Nitrative Stress In Skeletal Muscle Of Patients With Mitochondrial DNA Mutation
Neuromuscular and Clinical Neurophysiology (EMG)
P2 - Poster Session 2 (5:30 PM-6:30 PM)
12-039

To evaluate the presence of nitrated proteins in muscle samples from patients with mitochondrial diseases.

Antioxidants are commonly used in the treatment of patients with mitochondrial diseases, due to the increased generation of reactive oxygen species (ROS) in respiratory chain deficiencies.

Besides ROS, skeletal muscle also produces nitric oxide (NO), a free radical involved in the regulation of mitochondrial function as well as potential to generate nitrative stress caused by nitrogen radicals. The relevance of nitrative stress in mitochondrial diseases is still unknown.

 

We studied 29 samples obtained from patients with mtDNA mutations (multiple deletions, N=8; single deletions, N=7; point mutation, N=8), nuclear gene defects (N=6) and 4 controls. Nitrated proteins, markers of nitrative stress, were quantified and detected by immunofluorescence.
Immunoreactivity was detected in the sarcoplasm and/or sarcolemma. We found nitrated proteins on the sarcolemma in 24% of patients with proportions from 1,8% to 98% of affected fibers. Among these patients, three had the majority of fibers with nitrated sarcolemma: one with TK2 gene mutation (98.6%), one with m.3243A<G (94.6%) and one with m.3251A<G (53.2%). Sarcoplasmic immunoreactivity was found in 37% of patients but considering samples with ragged red fibers (RRF), only 3 (27%) had a significant increase of sarcoplasmic nitrated proteins in RRFs but all of them had mutations in the MT-TL1 gene encoding the tRNALeu(UUR). The intensity of sarcoplasmic immunoreactivity was not correlated with age, creatine kinase levels, percentage of RRF and COX negative fibers
Patients with mutations in the MT-TL1 gene presented the most affected muscle fibers with nitrated proteins suggesting that they are more predisposed to nitrative stress. Thus nitrative stress may be a potential target for treatment of mitochondrial diseases specially those affecting the tRNALeu(UUR). Supported by FAPESP, CAPES, CNPq
Authors/Disclosures
Jomenica D. Livramento (UNIFESP)
PRESENTER 		No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Beatriz H. Kiyomoto No disclosure on file
No disclosure on file
Acary S. Oliveira, MD (UNIFESP - Escuela Paulista De Medicina) No disclosure on file
Celia H. Tengan, MD (Universidade Federal De Sao Paulo) No disclosure on file