Published ahead of print on May 11, 2006, doi:10.1165/rcmb.2006-0097OC
© 2006 American Thoracic Society DOI: 10.1165/rcmb.2006-0097OC Increased Protein Arginine Methylation in Chronic HypoxiaRole of Protein Arginine MethyltransferasesDepartment of Medicine II, University of Giessen Lung Center, Justus-Liebig University Giessen, Giessen, Germany Correspondence and requests for reprints should be addressed to Oliver Eickelberg, M.D., University of Giessen Lung Center, Department of Medicine II, Aulweg 123, Room 6-11, D-35392 Giessen, Germany. E-mail: oliver.eickelberg{at}innere.med.uni-giessen.de Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthesis. ADMA is generated by catabolism of proteins containing methylated arginine residues, and its levels are correlated with endothelial dysfunction in systemic cardiovascular diseases. Arginine methylation of cellular proteins is catalyzed by protein arginine methyltransferases (PRMT). The expression and localization of PRMT in the lung has not been addressed. Here, we sought to analyze the expression of PRMT isoforms in the lung and to determine whether PRMT expression is altered during exposure to chronic hypoxia (10% oxygen). Adult mice were exposed to hypoxia for up to 3 wk, and lung tissues were harvested and processed for RT-PCR, Western blotting, immunohistochemistry, and determination of tissue ADMA levels. All PRMT isoforms investigated were detected at the mRNA and protein level in mouse lung, and were localized primarily to the bronchial and alveolar epithelium. In lungs of mice subjected to chronic hypoxia, PRMT2 mRNA and protein levels were up-regulated, whereas the expression of all other PRMT isoforms remained unchanged. This was mainly due to increased expression of PRMT2 in alveolar type II cells, which did not express detectable levels of PRMT2 under normoxic conditions. Consistent with these observations, lung ADMA levels and ADMA/L-Arginine ratios were increased under hypoxic conditions. These results demonstrate that PRMTs are expressed and functional in the lung, and that hypoxia is a potent regulator of PRMT2 expression and lung ADMA concentrations. These data suggest that structural and functional changes caused by hypoxia may be linked to ADMA metabolism.
Key Words: bronchial epithelium • immunohistochemistry • protein methylation • vessels This article has been cited by other articles:
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