Increased oxidative stress response in granulocytes from older patients with a hip fracture may account for slow regeneration

Zhiyong Wang, Sabrina Ehnert, Christoph Ihle, Lilianna Schyschka, Stefan Pscherer, Natascha C Nussler, Karl F Braun, Martijn Van Griensven, Guobin Wang, Rainer Burgkart, Ulrich Stöckle, Florian Gebhard, Helen Vester, Andreas K Nussler*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)819847
JournalOxidative Medicine and Cellular Longevity
Volume2014
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • Cell Survival/drug effects
  • Cellular Senescence/drug effects
  • Enzyme Activation/drug effects
  • Female
  • Granulocytes/drug effects
  • HEK293 Cells
  • HL-60 Cells
  • Hip Fractures/enzymology
  • Humans
  • Hydrogen Peroxide/toxicity
  • Lipid Peroxidation
  • Male
  • Middle Aged
  • Oxidative Stress/drug effects
  • Regeneration/drug effects
  • Serum/metabolism
  • Superoxide Dismutase/metabolism
  • Young Adult
  • p38 Mitogen-Activated Protein Kinases/metabolism

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