Endoplasmic Reticulum Stress Activation during Total Knee Arthroplasty.
Austin D Hocker1, Ryan M Boileau, Brick A Lantz
1Department of Human Physiology, University of Oregon, Eugene, OR, USA.
Physiological Reports
|October 26, 2013
Summary
Total knee arthroplasty (TKA) involves tourniquet-induced ischemia and reperfusion (I/R) injury. This study found that I/R activates all three branches of the endoplasmic reticulum unfolded protein response (UPR) in vastus lateralis muscle during TKA.
Area of Science:
- Orthopedics
- Molecular Biology
- Cellular Stress Response
Background:
- Total knee arthroplasty (TKA) is a common surgery for osteoarthritis, often using tourniquets that cause limb ischemia and reperfusion (I/R).
- The effects of I/R on muscle during TKA are not fully understood, but previous studies suggest altered cell stress and translation.
- Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are known consequences of I/R.
Purpose of the Study:
- To investigate the activation of the UPR in vastus lateralis muscle during TKA.
- To determine if ER stress markers are altered by tourniquet-induced I/R in the context of TKA.
Main Methods:
- Muscle biopsies were collected from the vastus lateralis at baseline, during maximal ischemia, and during reperfusion in patients undergoing TKA.
- Western blotting was used to assess the phosphorylation of translation initiation factors (4E-BP1, AKT, eIF2α) and ER stress markers (ATF6, CASP3).
- XBP1 splicing assays were performed to evaluate UPR activation.
Main Results:
- Ischemia during TKA led to decreased phosphorylation of 4E-BP1 and AKT, and increased eIF2α phosphorylation, indicating reduced translation initiation.
- Cleaved ATF6 increased during ischemia, while CASP3 activation increased during reperfusion.
- Increased spliced XBP1 transcripts were observed during ischemia, diminishing during reperfusion.
Conclusions:
- Ischemia and reperfusion during TKA activate all three branches of the ER stress response (UPR) in skeletal muscle.
- These findings highlight the cellular stress response to I/R injury in the context of TKA.
- Understanding the UPR activation may offer targets for mitigating I/R-related muscle damage during TKA.
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