Overexpression of antioxidant enzyme peroxiredoxin 5 protects human tendon cells against apoptosis and loss of cellular function during oxidative stress.
Oxidative stress and apoptosis are implicated in tendon degeneration. Peroxiredoxin 5 (PRDX5) is a novel thioredoxin peroxidase recently identified in mammals, participating directly in eliminating hydrogen peroxide (H(2)O(2)) and neutralizing other reactive oxygen species (ROS). We have previously reported that PRDX5 is upregulated in degenerative human tendon. However, the effects of this upregulation on human tendon cell function remain unknown, in particular, with regards to oxidative stress conditions. Here we report that exposure of human tendon cells to 50 microM H(2)O(2) for 24 h (in vitro oxidative stress) caused a significant increase in the percentage of apoptotic cells (P<0.05) as assessed by flow cytometric analysis of Annexin V binding, accompanied by increased PRXD5 mRNA and protein expression. Overexpression of PRDX5 in human tendon cells via transfection inhibited H(2)O(2)-induced tendon cell apoptosis by 46% (P<0.05), and prevented the decrease in tendon cell collagen synthesis which occurs under H(2)O(2) challenge, although the decrease in collagen synthesis was small. Results from our study indicate that the antioxidant enzyme PRDX5 plays a protective role in human tendon cells against oxidative stress by reducing apoptosis and maintaining collagen synthesis.
Orthopaedic Research Institute, St. George Hospital Campus, 4-10 South Street, University of New South Wales, Sydney, NSW 2217, Australia.
Jun
J
Yuan
George A C
GA
Murrell
Annette
A
Trickett
Marie
M
Landtmeters
Bernard
B
Knoops
Min-Xia
MX
Wang
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D003094:Collagen / Q000096:biosynthesis; D017931:DNA Primers; D005434:Flow Cytometry; D006801:Humans; D018384:Oxidative Stress; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D054464:Peroxiredoxins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013710:Tendons / Q000166:cytology*
D017304:Annexin A5; D017931:DNA Primers; D012333:RNA, Messenger; D003094:Collagen; D010544:Peroxidases; C515974:PRDX5 protein, human; D054464:Peroxiredoxins