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Attenuation of endoplasmic reticulum stress by caffeine ameliorates hyperoxia-induced lung injury. Am J Physiol Lung Cell Mol Physiol 2017 May 01;312(5):L586-L598

Date

02/19/2017

Pubmed ID

28213471

Pubmed Central ID

PMC5451596

DOI

10.1152/ajplung.00405.2016

Scopus ID

2-s2.0-85018731493 (requires institutional sign-in at Scopus site)   72 Citations

Abstract

Rodent pups exposed to hyperoxia develop lung changes similar to bronchopulmonary dysplasia (BPD) in extremely premature infants. Oxidative stress from hyperoxia can injure developing lungs through endoplasmic reticulum (ER) stress. Early caffeine treatment decreases the rate of BPD, but the mechanisms remain unclear. We hypothesized that caffeine attenuates hyperoxia-induced lung injury through its chemical chaperone property. Sprague-Dawley rat pups were raised either in 90 (hyperoxia) or 21% (normoxia) oxygen from postnatal day 1 (P1) to postnatal day 10 (P10) and then recovered in 21% oxygen until P21. Caffeine (20 mg/kg) or normal saline (control) was administered intraperitoneally daily starting from P2. Lungs were inflation-fixed for histology or snap-frozen for immunoblots. Blood caffeine levels were measured in treated pups at euthanasia and were found to be 18.4 ± 4.9 μg/ml. Hyperoxia impaired alveolar formation and increased ER stress markers and downstream effectors; caffeine treatment attenuated these changes at P10. Caffeine also attenuated the hyperoxia-induced activation of cyclooxygenase-2 and markers of apoptosis. In conclusion, hyperoxia-induced alveolar growth impairment is mediated, in part, by ER stress. Early caffeine treatment protects developing lungs from hyperoxia-induced injury by attenuating ER stress.

Author List

Teng RJ, Jing X, Michalkiewicz T, Afolayan AJ, Wu TJ, Konduri GG

Authors

Adeleye James Afolayan MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Xi-Gang Jing Research Scientist I in the Pediatrics department at Medical College of Wisconsin
Girija Ganesh Konduri MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
Ru-Jeng Teng MD Professor in the Pediatrics department at Medical College of Wisconsin
Tzong-Jin Wu MD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
Caffeine
Cyclooxygenase 2
Endoplasmic Reticulum Stress
Energy Metabolism
Female
Heat-Shock Proteins
Hyperoxia
Lung
Lung Injury
Mitochondria
Models, Biological
Neovascularization, Physiologic
Organelle Biogenesis
Oxidative Stress
Peroxidase
Pneumonia
Pulmonary Alveoli
Rats, Sprague-Dawley
Unfolded Protein Response