Cytoprotective Effect of Ferritin H in Renal Ischemia Reperfusion Injury.

Abstract

Oxidative stress is a major contributor to kidney injury following ischemia reperfusion. Ferritin, a highly conserved iron-binding protein, is a key protein in the maintenance of cellular iron homeostasis and protection from oxidative stress. Ferritin mitigates oxidant stress by sequestering iron and preventing its participation in reactions that generate reactive oxygen species. Ferritin is composed of two subunit types, ferritin H and ferritin L. Using an in vivo model that enables conditional tissue-specific doxycycline-inducible expression of ferritin H in the mouse kidney, we tested the hypothesis that an increased level of H-rich ferritin is renoprotective in ischemic acute renal failure. Prior to induction of ischemia, doxycycline increased ferritin H in the kidneys of the transgenic mice nearly 6.5-fold. Following reperfusion for 24 hours, induction of neutrophil gelatinous-associated lipocalin (NGAL, a urine marker of renal dysfunction) was reduced in the ferritin H overexpressers compared to controls. Histopathologic examination following ischemia reperfusion revealed that ferritin H overexpression increased intact nuclei in renal tubules, reduced the frequency of tubular profiles with luminal cast materials, and reduced activated caspase-3 in the kidney. In addition, generation of 4-hydroxy 2-nonenal protein adducts, a measurement of oxidant stress, was decreased in ischemia-reperfused kidneys of ferritin H overexpressers. These studies demonstrate that ferritin H can inhibit apoptotic cell death, enhance tubular epithelial viability, and preserve renal function by limiting oxidative stress following ischemia reperfusion injury.

• Authors: Heather C Hatcher, Lia Tesfay, Suzy V Torti, Frank M Torti
• Journal: PloS one (PLoS One) Vol. 10 Issue 9 Pg. e0138505 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26379029 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Aldehydes
• Iron-Binding Proteins
• Lipocalins
• 2-nonenal
• Apoferritins
• Caspase 3

Topics

• Acute Kidney Injury (drug therapy, metabolism)
• Aldehydes (metabolism)
• Animals
• Apoferritins (pharmacology)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cytoprotection (drug effects)
• Female
• Homeostasis (drug effects)
• Iron-Binding Proteins (metabolism)
• Ischemia (drug therapy, metabolism)
• Kidney Tubules (drug effects, metabolism)
• Lipocalins (metabolism)
• Male
• Mice
• Mice, Transgenic
• Oxidative Stress (drug effects)
• Reperfusion Injury (drug therapy, metabolism)