Effect of Chronic Alcohol Abuse on Anabolic and Catabolic Signaling Pathways in Human Skeletal Muscle

Boris S. Shenkman, Svetlana P. Belova, Olga E. Zinovyeva, Nudlya D. Samkhaeva, Timur M. Mirzoev, Natalia A. Vilchinskaya, Erzhena G. Altaeva, Olga V. Turtikova, Tatiana Kostrominova, Tatiana L. Nemirovskaya

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Animal studies showed that alcoholic myopathy is characterized by the reduction in myofiber cross-sectional area (CSA) and by impaired anabolic signaling. The goal of this study was to compare changes in CSA and fiber type composition with modifications in anabolic and catabolic signaling pathways at the early stages of alcohol misuse in humans. Methods: Skeletal muscle samples from 7 male patients with chronic alcohol abuse (AL; 47.7 ± 2.0 years old; alcohol misuse duration 7.7 ± 0.6 years) were compared with muscle from a control group of 7 healthy men (C; 39.7 ± 5.0 years old). Biopsies from vastus lateralis muscles were taken and analyzed for the changes in fiber type composition, fiber CSA, and for the alterations in anabolic and catabolic signaling pathways. Results: AL patients did not have detectable clinical myopathy symptoms or muscle fiber atrophy, but the relative proportion of fast fibers was increased. There was a significant decrease in IGF-1 in plasma and IRS-1 protein content in muscle of AL group. Levels of total and phosphorylated p70S6K1, GSK3β, and p90RSK1 were not different between AL and C groups. Muscle of AL patients had increased mRNA expression of HSP70 and HSP90. A marker of anabolic pathway p-4E-BP1 was decreased, while catabolic markers (MuRF-1, MAFbx, ubiquitinated proteins) were increased in AL patients when compared with C group. Conclusions: At the early stages of alcohol misuse in humans, changes in the regulation of anabolic and catabolic signaling pathways precede the development of skeletal muscle atrophy and manifestation of clinical symptoms of alcoholic myopathy.

Original languageEnglish (US)
JournalAlcoholism: Clinical and Experimental Research
DOIs
StateAccepted/In press - Jan 1 2017

Fingerprint

Alcoholism
Muscle
Skeletal Muscle
Muscular Diseases
Alcohols
Muscles
Muscular Atrophy
Fibers
Ubiquitinated Proteins
Quadriceps Muscle
Insulin-Like Growth Factor I
Biopsy
Control Groups
Messenger RNA
Chemical analysis
Animals
Proteins
Plasmas

Keywords

  • Ethanol
  • IGF-1
  • IRS-1
  • P70S6K1
  • P90RSK1
  • Ubiquitinated Proteins

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

Shenkman, B. S., Belova, S. P., Zinovyeva, O. E., Samkhaeva, N. D., Mirzoev, T. M., Vilchinskaya, N. A., ... Nemirovskaya, T. L. (Accepted/In press). Effect of Chronic Alcohol Abuse on Anabolic and Catabolic Signaling Pathways in Human Skeletal Muscle. Alcoholism: Clinical and Experimental Research. https://doi.org/10.1111/acer.13531

Effect of Chronic Alcohol Abuse on Anabolic and Catabolic Signaling Pathways in Human Skeletal Muscle. / Shenkman, Boris S.; Belova, Svetlana P.; Zinovyeva, Olga E.; Samkhaeva, Nudlya D.; Mirzoev, Timur M.; Vilchinskaya, Natalia A.; Altaeva, Erzhena G.; Turtikova, Olga V.; Kostrominova, Tatiana; Nemirovskaya, Tatiana L.

In: Alcoholism: Clinical and Experimental Research, 01.01.2017.

Research output: Contribution to journalArticle

Shenkman, BS, Belova, SP, Zinovyeva, OE, Samkhaeva, ND, Mirzoev, TM, Vilchinskaya, NA, Altaeva, EG, Turtikova, OV, Kostrominova, T & Nemirovskaya, TL 2017, 'Effect of Chronic Alcohol Abuse on Anabolic and Catabolic Signaling Pathways in Human Skeletal Muscle', Alcoholism: Clinical and Experimental Research. https://doi.org/10.1111/acer.13531
Shenkman, Boris S. ; Belova, Svetlana P. ; Zinovyeva, Olga E. ; Samkhaeva, Nudlya D. ; Mirzoev, Timur M. ; Vilchinskaya, Natalia A. ; Altaeva, Erzhena G. ; Turtikova, Olga V. ; Kostrominova, Tatiana ; Nemirovskaya, Tatiana L. / Effect of Chronic Alcohol Abuse on Anabolic and Catabolic Signaling Pathways in Human Skeletal Muscle. In: Alcoholism: Clinical and Experimental Research. 2017.
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abstract = "Background: Animal studies showed that alcoholic myopathy is characterized by the reduction in myofiber cross-sectional area (CSA) and by impaired anabolic signaling. The goal of this study was to compare changes in CSA and fiber type composition with modifications in anabolic and catabolic signaling pathways at the early stages of alcohol misuse in humans. Methods: Skeletal muscle samples from 7 male patients with chronic alcohol abuse (AL; 47.7 ± 2.0 years old; alcohol misuse duration 7.7 ± 0.6 years) were compared with muscle from a control group of 7 healthy men (C; 39.7 ± 5.0 years old). Biopsies from vastus lateralis muscles were taken and analyzed for the changes in fiber type composition, fiber CSA, and for the alterations in anabolic and catabolic signaling pathways. Results: AL patients did not have detectable clinical myopathy symptoms or muscle fiber atrophy, but the relative proportion of fast fibers was increased. There was a significant decrease in IGF-1 in plasma and IRS-1 protein content in muscle of AL group. Levels of total and phosphorylated p70S6K1, GSK3β, and p90RSK1 were not different between AL and C groups. Muscle of AL patients had increased mRNA expression of HSP70 and HSP90. A marker of anabolic pathway p-4E-BP1 was decreased, while catabolic markers (MuRF-1, MAFbx, ubiquitinated proteins) were increased in AL patients when compared with C group. Conclusions: At the early stages of alcohol misuse in humans, changes in the regulation of anabolic and catabolic signaling pathways precede the development of skeletal muscle atrophy and manifestation of clinical symptoms of alcoholic myopathy.",
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T1 - Effect of Chronic Alcohol Abuse on Anabolic and Catabolic Signaling Pathways in Human Skeletal Muscle

AU - Shenkman, Boris S.

AU - Belova, Svetlana P.

AU - Zinovyeva, Olga E.

AU - Samkhaeva, Nudlya D.

AU - Mirzoev, Timur M.

AU - Vilchinskaya, Natalia A.

AU - Altaeva, Erzhena G.

AU - Turtikova, Olga V.

AU - Kostrominova, Tatiana

AU - Nemirovskaya, Tatiana L.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background: Animal studies showed that alcoholic myopathy is characterized by the reduction in myofiber cross-sectional area (CSA) and by impaired anabolic signaling. The goal of this study was to compare changes in CSA and fiber type composition with modifications in anabolic and catabolic signaling pathways at the early stages of alcohol misuse in humans. Methods: Skeletal muscle samples from 7 male patients with chronic alcohol abuse (AL; 47.7 ± 2.0 years old; alcohol misuse duration 7.7 ± 0.6 years) were compared with muscle from a control group of 7 healthy men (C; 39.7 ± 5.0 years old). Biopsies from vastus lateralis muscles were taken and analyzed for the changes in fiber type composition, fiber CSA, and for the alterations in anabolic and catabolic signaling pathways. Results: AL patients did not have detectable clinical myopathy symptoms or muscle fiber atrophy, but the relative proportion of fast fibers was increased. There was a significant decrease in IGF-1 in plasma and IRS-1 protein content in muscle of AL group. Levels of total and phosphorylated p70S6K1, GSK3β, and p90RSK1 were not different between AL and C groups. Muscle of AL patients had increased mRNA expression of HSP70 and HSP90. A marker of anabolic pathway p-4E-BP1 was decreased, while catabolic markers (MuRF-1, MAFbx, ubiquitinated proteins) were increased in AL patients when compared with C group. Conclusions: At the early stages of alcohol misuse in humans, changes in the regulation of anabolic and catabolic signaling pathways precede the development of skeletal muscle atrophy and manifestation of clinical symptoms of alcoholic myopathy.

AB - Background: Animal studies showed that alcoholic myopathy is characterized by the reduction in myofiber cross-sectional area (CSA) and by impaired anabolic signaling. The goal of this study was to compare changes in CSA and fiber type composition with modifications in anabolic and catabolic signaling pathways at the early stages of alcohol misuse in humans. Methods: Skeletal muscle samples from 7 male patients with chronic alcohol abuse (AL; 47.7 ± 2.0 years old; alcohol misuse duration 7.7 ± 0.6 years) were compared with muscle from a control group of 7 healthy men (C; 39.7 ± 5.0 years old). Biopsies from vastus lateralis muscles were taken and analyzed for the changes in fiber type composition, fiber CSA, and for the alterations in anabolic and catabolic signaling pathways. Results: AL patients did not have detectable clinical myopathy symptoms or muscle fiber atrophy, but the relative proportion of fast fibers was increased. There was a significant decrease in IGF-1 in plasma and IRS-1 protein content in muscle of AL group. Levels of total and phosphorylated p70S6K1, GSK3β, and p90RSK1 were not different between AL and C groups. Muscle of AL patients had increased mRNA expression of HSP70 and HSP90. A marker of anabolic pathway p-4E-BP1 was decreased, while catabolic markers (MuRF-1, MAFbx, ubiquitinated proteins) were increased in AL patients when compared with C group. Conclusions: At the early stages of alcohol misuse in humans, changes in the regulation of anabolic and catabolic signaling pathways precede the development of skeletal muscle atrophy and manifestation of clinical symptoms of alcoholic myopathy.

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KW - IGF-1

KW - IRS-1

KW - P70S6K1

KW - P90RSK1

KW - Ubiquitinated Proteins

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