Journal article
Ferrous iron is found in mesenteric lymph bound to TIMP-2 following hemorrhage/resuscitation
Biometals, v 24(2), pp 279-289
01 Apr 2011
PMID: 21229381
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Extracellular iron has been implicated in the pathogenesis of post-injury organ failure. However, the source(s) and biochemical species of this iron have not been identified. Based upon evidence that distant organ injury results from an increase in intestinal permeability, we looked for ferrous iron in mesenteric lymph in anesthetized rats undergoing hemorrhage and fluid resuscitation (H/R). Ferrous iron increased in lymph from 4.7 nmol/mg of protein prior to hemorrhage to 86.6 nmol/mg during resuscitation. Utilizing immuno-spin trapping in protein fractions that were rich in iron, we tentatively indentified protein carrier(s) of ferrous iron by MALDI-TOF MS. One of the identified proteins was the metalloproteinase (MMP) inhibitor, TIMP-2. Antibody to TIMP-2 immunoprecipitated 74% of the ferrozine detectable iron in its protein fraction. TIMP-2 binds iron in vitro at pH 6.3, which is typical of conditions in the mesentery during hemorrhage, but it retains the ability to inhibit the metalloproteases MMP-2 and MMP-9. In summary, there is a large increase in extracellular ferrous iron in the gut in H/R demonstrating dysregulation of iron homeostasis. We have identified, for the first time, the binding of extracellular iron to TIMP-2.
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Details
- Title
- Ferrous iron is found in mesenteric lymph bound to TIMP-2 following hemorrhage/resuscitation
- Creators
- James L. Atkins - Walter Reed Army Institute of ResearchNikolai V. Gorbunov - Henry M. Jackson FoundationValerie Trabosh - Walter Reed Army Institute of ResearchRachel Van Duyne - George Mason UniversityFatah Kashanchi - George Mason UniversityAndrei M. Komarov - Washington University Medical Center
- Publication Details
- Biometals, v 24(2), pp 279-289
- Publisher
- Springer Nature
- Number of pages
- 11
- Grant note
- PR033201 / Department of the Army
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000288387700008
- Scopus ID
- 2-s2.0-79959519378
- Other Identifier
- 991021902522304721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology