Open AccessEndoplasmic reticulum stress activation during total knee arthroplasty
Author(s) -
Hocker Austin D.,
Boileau Ryan M.,
Lantz Brick A.,
Jewett Brian A.,
Gilbert Jeffrey S.,
Dreyer Hans C.
Publication year - 2013
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.1002/phy2.52
Subject(s) - endoplasmic reticulum , total knee arthroplasty , unfolded protein response , medicine , microbiology and biotechnology , chemistry , bioinformatics , biology , surgery
Total knee arthroplasty ( TKA ) is the most common remediation for knee pain from osteoarthritis ( OA ) and is performed 650,000 annually in the U.S. A tourniquet is commonly used during TKA which causes ischemia and reperfusion (I/R) to the lower limb but the effects of I/R on muscle are not fully understood. Previous reports suggest upregulation of cell stress and catabolism and downregulation of markers of cap‐dependent translation during and after TKA . I/R has also been shown to cause endoplasmic reticulum ( ER ) stress and induce the unfolded protein response ( UPR ). We hypothesized that the UPR would be activated in response to ER stress during TKA . We obtained muscle biopsies from the vastus lateralis at baseline, before TKA ; at maximal ischemia, prior to tourniquet deflation; and during reperfusion in the operating room. Phosphorylation of 4E‐BP1 and AKT decreased during ischemia (−28%, P < 0.05; −20%, P < 0.05, respectively) along with an increase in eIF2α phosphorylation (64%, P < 0.05) suggesting decreased translation initiation. Cleaved ATF6 protein increased in ischemia (39%, P = 0.056) but returned to baseline during reperfusion. CASP3 activation increased during reperfusion compared to baseline (23%, P < 0.05). XBP1 splicing assays revealed an increase in spliced transcript during ischemia (31%, P < 0.05) which diminished during reperfusion. These results suggest that in response to I/R during TKA all three branches of the ER stress response are activated.