The effect of advanced glycation end products on cellular signaling molecules in skeletal muscle

Access this Article

Search this Article

Author(s)

    • Egawa Tatsuro Egawa Tatsuro
    • Laboratory of Health and Exercise Sciences, Graduate School of Human and Environmental Studies, Kyoto University|Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University|Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University
    • Goto Ayumi Goto Ayumi
    • Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University|Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University
    • Ito Rika Ito Rika
    • Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University
    • Goto Katsumasa Goto Katsumasa
    • Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University|Laboratory of Physiology, School of Health Sciences, Toyohashi SOZO University

Abstract

The accumulation of advanced glycation end products (AGEs) in the body causes the pathogenesis of aging-related diseases by inhibiting the normal properties and functions of proteins and the modulation of cellular signal transduction. Glycation stress induced by AGEs accumulation has the potential to contribute to sarcopenia: age-related reductions in muscle mass, strength, and function. However, the molecular response to AGEs in skeletal muscle is not fully understood. Therefore, to understand changes in cellular signaling in response to AGEs, this study aimed to investigate the phosphorylation status of phosphoproteins in AGEs-treated skeletal muscle. Treatment of C2C12 skeletal muscle cells with glucose-induced AGEs (0.1 mg/mL) for 5 days suppressed myotube formation, and this was accompanied by Nε-carboxymethyl-lysine accumulation. Reverse phase protein array analysis revealed that treatment with AGEs (glyoxylic-, pyruvate-, glycolaldehyde-, and glucose-induced AGEs) increased phosphorylation at eight phosphorylation sites and decreased phosphorylation at 64 phosphorylation sites. The phosphorylation level of signal transducer and activator of transcription 3 (STAT3) Tyr⁷⁰⁵ was most enhanced, and that of extracellular signal-regulated kinase (ERK) Thr²⁰²/Tyr²⁰⁴ was most suppressed. Almost all phosphorylation sites related to insulin/insulin-like growth factor 1 signaling were downregulated by AGEs. Increased STAT3 Tyr⁷⁰⁵ phosphorylation and decreased ERK Thr²⁰²/Tyr²⁰⁴ phosphorylation were observed in the skeletal muscles of mice treated with a diet high in AGEs for 16 weeks. These findings suggest that AGE accumulation impairs cellular signal transduction pathways in skeletal muscle cells, and thereby has the potential to induce skeletal muscle loss.

<p>The accumulation of advanced glycation end products (AGEs) in the body causes the pathogenesis of aging-related diseases by inhibiting the normal properties and functions of proteins and the modulation of cellular signal transduction. Glycation stress induced by AGEs accumulation has the potential to contribute to sarcopenia: age-related reductions in muscle mass, strength, and function. However, the molecular response to AGEs in skeletal muscle is not fully understood. Therefore, to understand changes in cellular signaling in response to AGEs, this study aimed to investigate the phosphorylation status of phosphoproteins in AGEs-treated skeletal muscle. Treatment of C2C12 skeletal muscle cells with glucose-induced AGEs (0.1 mg/mL) for 5 days suppressed myotube formation, and this was accompanied by Nε-carboxymethyl-lysine accumulation. Reverse phase protein array analysis revealed that treatment with AGEs (glyoxylic-, pyruvate-, glycolaldehyde-, and glucose-induced AGEs) increased phosphorylation at eight phosphorylation sites and decreased phosphorylation at 64 phosphorylation sites. The phosphorylation level of signal transducer and activator of transcription 3 (STAT3) Tyr<sup>705</sup> was most enhanced, and that of extracellular signal-regulated kinase (ERK) Thr<sup>202</sup>/Tyr<sup>204</sup> was most suppressed. Almost all phosphorylation sites related to insulin/insulin-like growth factor 1 signaling were downregulated by AGEs. Increased STAT3 Tyr<sup>705</sup> phosphorylation and decreased ERK Thr<sup>202</sup>/Tyr<sup>204</sup> phosphorylation were observed in the skeletal muscles of mice treated with a diet high in AGEs for 16 weeks. These findings suggest that AGE accumulation impairs cellular signal transduction pathways in skeletal muscle cells, and thereby has the potential to induce skeletal muscle loss.</p>

Journal

  • The Journal of Physical Fitness and Sports Medicine

    The Journal of Physical Fitness and Sports Medicine 7(4), 229-238, 2018

    The Japanese Society of Physical Fitness and Sports Medicine

Codes

  • NII Article ID (NAID)
    130007406072
  • NII NACSIS-CAT ID (NCID)
    AA12573156
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    2186-8131
  • NDL Article ID
    029129902
  • NDL Call No.
    Z76-A776
  • Data Source
    NDL  IR  J-STAGE 
Page Top