Increased oxidative stress response in granulocytes from older patients with a hip fracture may account for slow regeneration.
Proximal femur fracture, a typical fracture of the elderly, is often associated with morbidity, reduced quality of life, impaired physical function and increased mortality. There exists evidence that responses of the hematopoietic microenvironment to fractures change with age. Therefore, we investigated oxidative stress markers and oxidative stress-related MAPK activation in granulocytes from the young and the elderly with and without fractured long bones. Lipid peroxidation levels were increased in the elderly controls and patients. Aged granulocytes were more sensitive towards oxidative stress induced damage than young granulocytes. This might be due to the basally increased expression of SOD-1 in the elderly, which was not further induced by fractures, as observed in young patients. This might be caused by an altered MAPK activation. In aged granulocytes basal p38 and JNK activities were increased and basal ERK1/2 activity was decreased. Following fracture, JNK activity decreased, while ERK1/2 and p38 activities increased in both age groups. Control experiments with HL60 cells revealed that the observed p38 activation depends strongly on age. Summarizing, we observed age-dependent changes in the oxidative stress response system of granulocytes after fractures, for example, altered MAPK activation and SOD-1 expression. This makes aged granulocytes vulnerable to the stress stimuli of the fracture and following surgery.
Traumatology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 München, Germany ; Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Zhiyong
Z
Wang
Siegfried Weller Institute for Trauma Research, BG Trauma Center Tübingen, Eberhard Karls University Tübingen, Schnarrenbergstraße 95, 72076 Tübingen, Germany.
Sabrina
S
Ehnert
Siegfried Weller Institute for Trauma Research, BG Trauma Center Tübingen, Eberhard Karls University Tübingen, Schnarrenbergstraße 95, 72076 Tübingen, Germany.
Christoph
C
Ihle
Traumatology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 München, Germany.
Lilianna
L
Schyschka
Department of Diabetology, Klinikum Traunstein, Cuno-Niggl-Straße 3, 83278 Traunstein, Germany.
Stefan
S
Pscherer
Department of Surgery, Neuperlach Hospital, Städtisches Klinikum München GmbH, Oskar-Maria-Graf-Ring 51, 81737 München, Germany.
Natascha C
NC
Nussler
Traumatology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 München, Germany.
Karl F
KF
Braun
Traumatology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 München, Germany.
Martijn
M
Van Griensven
Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Guobin
G
Wang
Clinic for Orthopedy, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 München, Germany.
Rainer
R
Burgkart
Siegfried Weller Institute for Trauma Research, BG Trauma Center Tübingen, Eberhard Karls University Tübingen, Schnarrenbergstraße 95, 72076 Tübingen, Germany.
Ulrich
U
Stöckle
Department of Trauma, Hand, Plastic and Reconstructive Surgery, Albert-Einstein University Ulm, Albert-Einstein-Allee 39, 89081 Ulm, Germany.
Florian
F
Gebhard
Traumatology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 München, Germany.
Helen
H
Vester
Siegfried Weller Institute for Trauma Research, BG Trauma Center Tübingen, Eberhard Karls University Tübingen, Schnarrenbergstraße 95, 72076 Tübingen, Germany.
Andreas K
AK
Nussler
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D057809:HEK293 Cells; D018922:HL-60 Cells; D006620:Hip Fractures / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D012038:Regeneration / Q000187:drug effects; D044967:Serum / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases