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Cross talk between NADPH oxidase and autophagy in pulmonary artery endothelial cells with intrauterine persistent pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2012 Apr 01;302(7):L651-63

Date

01/17/2012

Pubmed ID

22245997

Pubmed Central ID

PMC3330765

DOI

10.1152/ajplung.00177.2011

Scopus ID

2-s2.0-84859447737   56 Citations

Abstract

Autophagy is a process for cells to degrade proteins or entire organelles to maintain a balance in the synthesis, degradation, and subsequent recycling of cellular products. Increased reactive oxygen species formation is known to induce autophagy. We previously reported that increased NADPH oxidase (NOX) activity in pulmonary artery endothelial cells (PAEC) from fetal lambs with persistent pulmonary hypertension (PPHN) contributes to impaired angiogenesis in PPHN-PAEC compared with normal PAEC. We hypothesized that increased NOX activity in PPHN-PAEC is associated with increased autophagy, which, in turn, contributes to impaired angiogenesis in PPHN-PAEC. In the present study, we detected increased autophagy in PPHN-PAEC as shown by increased ratio of the microtubule-associated protein 1 light chain (LC3)-II to LC3-I and increased percentage of green fluorescent protein-LC3 punctate positive cells. Inhibiting autophagy by 3-methyladenine, chloroquine, and beclin-1 knockdown in PPHN-PAEC has led to decreased autophagy and increased in vitro angiogenesis. Inhibition of autophagy also decreased the association between gp91(phox) and p47(phox), NOX activity, and superoxide generation. A nonspecific antioxidant N-acetylcysteine and a NOX inhibitor apocynin decreased autophagy in PPHN-PAEC. In conclusion, autophagy may contribute to impaired angiogenesis in PPHN-PAEC through increasing NOX activity. Our results suggest that, in PPHN-PAEC, a positive feedback relationship between autophagy and NOX activity may regulate angiogenesis.

Author List

Teng RJ, Du J, Welak S, Guan T, Eis A, Shi Y, Konduri GG

Authors

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
Scott R. Welak MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin




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

Adenine
Animals
Apoptosis Regulatory Proteins
Autophagy
Cells, Cultured
Chloroquine
Endothelial Cells
Endothelium, Vascular
Green Fluorescent Proteins
Hypertension, Pulmonary
Microtubule-Associated Proteins
NADPH Oxidases
Neovascularization, Physiologic
Nuclear Proteins
Pulmonary Artery
Reactive Oxygen Species
Receptors, Immunologic
Recombinant Fusion Proteins
Sheep
jenkins-FCD Prod-480 9a4deaf152b0b06dd18151814fff2e18f6c05280