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Caffeine ameliorates hyperoxia-induced lung injury by protecting GCH1 function in neonatal rat pups. Pediatr Res 2017 Sep;82(3):483-489

Date

04/12/2017

Pubmed ID

28399119

Pubmed Central ID

PMC5570644

DOI

10.1038/pr.2017.89

Scopus ID

2-s2.0-85028332881   13 Citations

Abstract

BackgroundBronchopulmonary dysplasia (BPD) is a major morbidity in premature infants, and impaired angiogenesis is considered a major contributor to BPD. Early caffeine treatment decreases the incidence of BPD; the mechanism remains incompletely understood.MethodsSprague-Dawley rat pups exposed to normoxia or hyperoxia since birth were treated daily with either 20 mg/kg caffeine or normal saline by an intraperitoneal injection from day 2 of life. The lungs were obtained for studies at days 10 and 21.ResultsHyperoxia impaired somatic growth and lung growth in the rat pups. The impaired lung growth during hyperoxia was associated with decreased levels of cyclic AMP (cAMP) and tetrahydrobiopterin (BH4) in the lungs. Early caffeine treatment increased cAMP levels in the lungs of hyperoxia-exposed pups. Caffeine also increased the levels of phosphorylated endothelial nitric oxide synthase (eNOS) at serine1177, total and serine51 phosphorylated GTP cyclohydrolase 1 (GCH1), and BH4 levels, with improved alveolar structure and angiogenesis in hyperoxia-exposed lungs. Reduced GCH1 levels in hyperoxia were due, in part, to increased degradation by the ubiquitin-proteasome system.ConclusionOur data support the notion that early caffeine treatment can protect immature lungs from hyperoxia-induced damage by improving eNOS activity through increased BH4 bioavailability.

Author List

Jing X, Huang YW, Jarzembowski J, Shi Y, Konduri GG, Teng RJ

Authors

Jason A. Jarzembowski MD, PhD Vice Chair, Chief, Professor in the Pathology 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 Associate Professor in the Pediatrics department at Medical College of Wisconsin




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

Animals
Animals, Newborn
Caffeine
Cyclic AMP
Female
GTP Cyclohydrolase
Hyperoxia
Lung Injury
Pregnancy
Rats
Rats, Sprague-Dawley
Weight Gain
jenkins-FCD Prod-480 9a4deaf152b0b06dd18151814fff2e18f6c05280