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Abstract: TH-PO262

Skeletal Muscle Chaperone and Co-Chaperone Proteins Are Elevated in Maintenance Hemodialysis Patients

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Fang, Hsin-Yu, University of Illinois Urbana-Champaign, Urbana, Illinois, United States
  • Van vliet, Stephan, Duke University, Durham, North Carolina, United States
  • Salvador, Amadeo F., University of Illinois Urbana-Champaign, Urbana, Illinois, United States
  • McKenna, Colleen F., University of Illinois Urbana-Champaign, Urbana, Illinois, United States
  • Burd, Nicholas A., University of Illinois Urbana-Champaign, Urbana, Illinois, United States
  • Wilund, Kenneth Robert, University of Illinois Urbana-Champaign, Urbana, Illinois, United States
Background

Various chaperone and co-chaperone proteins are required for the assembly and maintenance of the sarcomere to allow for maintenance of muscle tissue. We have previously established that both myofibrillar protein synthesis rates and markers of proteolysis are elevated in patients on maintenance hemodialysis (HD) when compared to BMI-matched controls. This result potentially underpins poor structural integrity that ultimately leads to poor physical performance in HD patients. Therefore, we aimed to determine whether HD patients have a higher abundance of chaperone and co-chaperone proteins involved in sarcomere integrity as compared to age- and BMI-matched controls.

Methods

Six HD patients (sex: 83.3% male; age: 58±13 y; BMI: 32±7 kg/m2) and six controls (sex: 66.7% male; age: 51±7 y; BMI: 31±4 kg/m2) received biopsies from the vastus lateralis after an overnight fast on a non-dialysis day to assess the relative protein content of Unc45b, Smyd1, Stub1, MuRF1, Hsp40, Hsp70, Hsp90α, and αβ-crystallin by Western blotting. We also determined plasma C-reactive protein (CRP) concentrations by ELISA. Pearson's correlation coefficient or the Spearman correlation coefficient were used to test the associations between systemic inflammation and sarcomere integrity.

Results

The skeletal muscle protein contents of Stub1 (P=0.032), MuRF1 (P=0.025), Hsp40 (P=0.039), and αβ-crystallin (P=0.019) were all elevated in HD patients when compared to controls, but the protein expressions of Unc45b (P=0.073), Smyd1 (P=0.922), Hsp70 (P=0.636), and Hsp90α (P=0.434) were not different. Among the four chaperones and co-chaperones whose protein expressions increased in HD patients, Stub1 (rs=0.833, P=0.010) and Hsp40 (r=0.896, P=0.003) were positively correlated with plasma CRP concentrations. However, neither MuRF1(rs=0.450, P=0.224) nor αβ-crystallin (rs=0.417, P=0.265) were associated with plasma CRP concentrations.

Conclusion

We demonstrated that the protein expression of several chaperones and co-chaperones in skeletal muscle were upregulated and positively correlated with the level of systemic inflammation in HD patients. Future studies are required to identify if dampening the inflammatory and uremic milieu can restore the regulation of muscle mass to a more ‘normal-state’ in HD patients.

Funding

  • Commercial Support