Indiana University School of Optometry
Faculty Research: Joseph A. Bonanno, OD, PhD
Hypoxia Preconditioning and Apoptosis

Mild forms of stress (e.g., ischemia, hypoxia, growth factor deprivation, oxidative stress) that do not reach the threshold for damaging cells can often be used as a preconditioning treatment that will protect cells from more intense damaging stress relative to cells that did not receive the preconditioning. We have found that hypoxia preconditioning will protect corneal keratocytes (and epithelial cells) from UV radiation. Typically cells that are exposed to two minutes of broad spectrum UV show high rates of apoptosis (80%), but cells that were preconditioned with 6 hours of 0.5% O2, show only 15% apoptosis.

Our hypothesis is that hypoxia activates at least two signal transduction pathways: HIFα (Hypoxia Inducible Factor 1a) and NFKB. NFKB activation acts to reduce the tumor suppressor PTEN leading to increased activity of the PI-3K signal transduction pathway and Akt (Protein kinase B). Akt phosphorylates and stabilizes HIF1α, which binds to HREs (hypoxia response elements) leading to expression and production of growth factors. Autocrine and paracrine activation of growth factor receptors stimulate RAS-MAPK and/or PI-3K pathways forming a positive feedback loop.

text following image describes picture

Cultured bovine keratocytes were exposed to normal air/5%CO2 incubation or 1.5%/5%CO2 for 6 hours. Cells were then exposed to normal conditions for 2 hours and then irradiated with UV for 8 minutes. Live-Dead staining was done 6 hours later. A-C: Control keratocytes A, DAPI: B, Live calcein; C, Dead ethidium homodimer. D-F Hypoxia preconditioned keratocytes. D, DAPI; E, Live; F, Dead. Bar graph summarizes Live-Dead staining.

Recent Publication

Hypoxia preconditioning protects corneal stromal cells against induced apoptosis. Dongmei Xing, Xingcai Sun, Jinhua Li, Miao Cui, Kah Tan-Allen and Joseph A. Bonanno; Exp Eye Res 2006; 82:780.

Lab Personnel

Tracy Nguyen
Tracy Nguyen		 Cailing Liu
Cailing Liu		 Supriya Jalimarada
Supriya
Jalimarada

 Ken Iwadate
Ken Iwadate

Go to: Dr. Bonanno's faculty page
IU Optometry home page

URL: http://www.opt.indiana.edu/people/faculty/bonanno/hypoxia.htm
Revised: July 24, 2009
IU Optometry home page: http://www.opt.indiana.edu/
Comments: Web Administrator
Copyright © 2009, The Trustees of Indiana University