Down-regulation of glutatione S-transferase α 4 (hGSTA4) in the muscle of thermally injured patients is indicative of susceptibility to bacterial infection
| Autor: | Apidianakis, Yiorgos, Que, Y. -A, Xu, W., Tegos, G. P., Zimniak, P., Hamblin, M. R., Tompkins, R. G., Xiao, W., Rahme, L. G. |
|---|---|
| Přispěvatelé: | Apidianakis, Yiorgos [0000-0002-7465-3560] |
| Rok vydání: | 2011 |
| Předmět: |
muscle
medicine.disease_cause Biochemistry Research Communications Lipid peroxidation chemistry.chemical_compound Mice burn Longitudinal Studies Prospective Studies Bacteria (microorganisms) Pathogen Glutathione Transferase Mice Knockout Mus article Bacterial Infections glutathione transferase A4 Thermal burn adipose tissue female priority journal Pseudomonas aeruginosa Mammalia Pseudomonas infection Female Disease Susceptibility medicine.symptom Burns down regulation Biotechnology skin Mice 129 Strain prevalence animal experiment Down-Regulation Context (language use) Inflammation Biology Trauma 4-Hydroxynonenal Genetics medicine Animals Humans controlled study Pseudomonas Infections infection sensitivity Muscle Skeletal 4 hydroxynonenal Molecular Biology mouse DNA Primers Aldehydes nonhuman catalysis Base Sequence animal model Biomarker Glutathione 4-hydroxynonenal Disease Models Animal chemistry Oxidative stress Case-Control Studies Immunology gene expression Wound Infection Murinae Reactive oxygen species |
| Zdroj: | FASEB Journal FASEB J. |
| ISSN: | 1530-6860 |
| Popis: | Patients with severe burns are highly susceptible to bacterial infection. While immunosuppression facilitates infection, the contribution of soft tissues to infection beyond providing a portal for bacterial entry remains unclear. We showed previously that glutathione S-transferase S1 (gstS1), an enzyme with conjugating activity against the lipid peroxidation byproduct 4-hydroxynonenal (4HNE), is important for resistance against wound infection in Drosophila muscle. The importance of the mammalian functional counterpart of GstS1 in the context of wounds and infection has not been investigated. Here we demonstrate that the presence of a burn wound dramatically affects expression of both human (hGSTA4) and mouse (mGsta4) 4HNE scavengers. hGSTA4 is down-regulated significantly within 1 wk of thermal burn injury in the muscle and fat tissues of patients from the large-scale collaborative Inflammation and the Host Response to Injury multicentered study. Similarly, mGsta4, the murine GST with the highest catalytic efficiency for 4HNE, is down-regulated to approximately half of normal levels in mouse muscle immediately postburn. Consequently, 4HNE protein adducts are increased 4- to 5-fold in mouse muscle postburn. Using an open wound infection model, we show that deletion of mGsta4 renders mice more susceptible to infection with the prevalent wound pathogen Pseudomonas aeruginosa, while muscle hGSTA4 expression negatively correlates with burn wound infection episodes per patient. Our data suggest that hGSTA4 down-regulation and the concomitant increase in 4HNE adducts in human muscle are indicative of susceptibility to infection in individuals with severely thermal injuries.—Apidianakis, Y., Que, Y.-A., Xu, W., Tegos, G. P., Zimniak, P., Hamblin, M. R., Tompkins, R. G., Xiao, W., Rahme, L. G. Down-regulation of glutatione S-transferase α 4 (hGSTA4) in the muscle of thermally injured patients is indicative of susceptibility to bacterial infection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text