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Change in the content of titin and nebulin and their phosphorylation level in the quadriceps femoris muscle in chronic alcoholic myopathy

https://doi.org/10.14412/2074-2711-2019-1-21-27

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Abstract

Objective: to assess the structural and functional state of skeletal muscles in the hip, as well as changes in the content of the sarcomere cytoskeleton proteins titin and nebulin and their phosphorylation level in patients with chronic alcohol intoxication.

Patients and methods. Thirteen patients (4 men and 9 women; mean age, 38.9±9.9 years) with chronic alcohol intoxication were examined. The average duration of regular consumption of alcoholic beverages was 7.6±3.7 years. The mean amount of alcohol consumed per week was 48.2±13.1 units. A control group included 10 healthy volunteers matched for age and sex. A neurological examination was performed according to the generally accepted scheme. Laboratory tests involved blood biochemical analysis estimating the levels of liver enzymes, creatine phosphokinase (CPK), and insulin-like growth factor-1 (IGF-1). All the patients underwent hip magnetic resonance imaging (MRI), followed by assessment of the degree of muscle tissue damage and by determination of the volume of anterior and posterior thigh muscles. The content of titin and nebulin and their phosphorylation level were determined in the muscle tissue samples obtained by an open biopsy from the lateral head of the quadriceps femoris muscle.

Results and discussion. Four (30.8%) patients were found to have proximal leg muscle weakness; the degree of paresis was the same in the anterior and posterior thigh muscles. There was a significant increase in the plasma level of liver enzymes; the CPK level remained within the reference values; there was a tendency towards lower IGF-1 levels. Analysis of MRI data showed that 7 (53.8%) patients had fatty degeneration in the thigh muscles. Quantitative evaluation ascertained a significant symmetrical decrease in the volume of anterior thigh muscles and a tendency towards a symmetrical reduction in that in the posterior thigh muscle compared to the control. Analysis of the content of titin and nebulin in the lateral head of the quadriceps femoris muscle revealed a significant decrease in the percentage of nebulin (81.1%; p < 0.01) and intact titin-1 (T1) isoforms (83.6%; p < 0.01). The percentage of proteolytic titin-2 (T2) fragments in the muscle of patients did not differ significantly from that in the control group. Estimating the phosphorylation level of the structural muscle proteins showed no significant differences when compared to the control.

Conclusion. Anterior and posterior thigh muscle weakness should be considered as the main clinical manifestation of chronic alcoholic myopathy (CAM) in the absence of biochemical and neurophysiological markers of the disease. Lower extremity muscle MRI that can reveal a lower muscle volume concurrent with fatty degeneration is a non-invasive informative diagnostic technique for CAM. The pathogenesis of skeletal muscle atrophy in chronic alcohol intoxication involves the sarcomere structural proteins titin and nebulin, which regulate the interaction of the major contractile proteins actin and myosin, and whole muscle contraction.

About the Authors

O. E. Zinovyeva
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia
Russian Federation

Department of Nervous System Diseases and Neurosurgery, Faculty of General Medicine 

11, Rossolimo St., Build. 1, Moscow 119021



N. D. Samkhaeva
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia
Russian Federation

Nyudlya Dordzhievna Samkhaeva

Clinic of Nervous System Diseases

11, Rossolimo St., Build. 1, Moscow 119021



I. M. Vikhlyantsev
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences; Pushchino State Institute of Natural Sciences, Ministry of Education and Science of Russia
Russian Federation
3, Institutskaya St., Pushchino, Moscow Region 142290, 3, Prospect Nauki, Pushchino, Moscow Region 142290


A. D. Ulanova
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences Pushchino State Institute of Natural Sciences, Ministry of Education and Science of Russia
Russian Federation
3, Institutskaya St., Pushchino, Moscow Region 142290, 3, Prospect Nauki, Pushchino, Moscow Region 142290


G. Z. Mikhailova
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences; Pushchino State Institute of Natural Sciences, Ministry of Education and Science of Russia
Russian Federation
3, Institutskaya St., Pushchino, Moscow Region 142290, 3, Prospect Nauki, Pushchino, Moscow Region 142290


N. S. Shcheglova
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia
Russian Federation

Clinic of Nervous System Diseases

11, Rossolimo St., Build. 1, Moscow 119021



D. O. Kazakov
Separate Structural Unit «Acad. Yu.E. Veltishchev Research Clinical Institute of Pediatrics», N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation
1, Ostrovityanov St., Moscow 117997


A. Yu. Emelyanova
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia
Russian Federation

Clinic of Nervous System Diseases

11, Rossolimo St., Build. 1, Moscow 119021



A. M. Nosovsky
State Research Center of the Russian Federation, Institute of Biomedical Problems, Russian Academy of Sciences
Russian Federation
76A, Khoroshevskoe Shosse, Moscow 123007


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For citation:


Zinovyeva O.E., Samkhaeva N.D., Vikhlyantsev I.M., Ulanova A.D., Mikhailova G.Z., Shcheglova N.S., Kazakov D.O., Emelyanova A.Y., Nosovsky A.M. Change in the content of titin and nebulin and their phosphorylation level in the quadriceps femoris muscle in chronic alcoholic myopathy. Neurology, Neuropsychiatry, Psychosomatics. 2019;11(1):21-27. (In Russ.) https://doi.org/10.14412/2074-2711-2019-1-21-27

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ISSN 2074-2711 (Print)
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