RGD Reference Report - Pneumocystis mediates overexpression of antizyme inhibitor resulting in increased polyamine levels and apoptosis in alveolar macrophages. - Rat Genome Database

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Pneumocystis mediates overexpression of antizyme inhibitor resulting in increased polyamine levels and apoptosis in alveolar macrophages.

Authors: Liao, Chung-Ping  Lasbury, Mark E  Wang, Shao-Hung  Zhang, Chen  Durant, Pamela J  Murakami, Yasuko  Matsufuji, Senya  Lee, Chao-Hung 
Citation: Liao CP, etal., J Biol Chem. 2009 Mar 20;284(12):8174-84. doi: 10.1074/jbc.M805787200. Epub 2009 Jan 20.
RGD ID: 14700806
Pubmed: (View Article at PubMed) PMID:19158080
DOI: Full-text: DOI:10.1074/jbc.M805787200

Pneumocystis pneumonia (PcP) is the most common opportunistic disease in immunocompromised patients. Alveolar macrophages are responsible for the clearance of Pneumocystis organisms; however, they undergo a high rate of apoptosis during PcP due to increased intracellular polyamine levels. In this study, the sources of polyamines and mechanisms of polyamine increase and polyamine-induced apoptosis were investigated. The level of ornithine decarboxylase (ODC) was elevated in alveolar macrophages, and the number of alveolar macrophages that took up exogenous polyamines was increased 20-fold during PcP. Monocytes, B lymphocytes, and CD8+ T lymphocytes that were recruited into the lung during PcP expressed high levels of ornithine decarboxylase, suggesting that these cells are sources of polyamines. Both protein and mRNA levels of antizyme inhibitor (AZI) were increased in alveolar macrophages during PcP. This AZI overexpression correlated with increased polyamine uptake by alveolar macrophages, because AZI expression knockdown decreased the polyamine uptake ability of these cells. AZI expression knockdown also decreased the apoptosis rate of alveolar macrophages. Pneumocystis organisms and zymosan A were found to induce AZI overexpression in alveolar macrophages, suggesting that beta-glucan, which is the major component of the Pneumocystis cell wall, induces AZI overexpression. The levels of mRNA, protein, and activity of polyamine oxidase were increased in alveolar macrophages during PcP, indicating that the H(2)O(2) generated during polyamine catabolism caused alveolar macrophages to undergo apoptosis. Taken together, results of this study indicate that Pneumocystis organisms induce AZI overexpression in alveolar macrophages, leading to increased polyamine synthesis and uptake and apoptosis rate of these cells.

Annotation

Disease Annotations    
pneumocystosis  (IEP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Azin1  (antizyme inhibitor 1)

Genes (Mus musculus)
Azin1  (antizyme inhibitor 1)

Genes (Homo sapiens)
AZIN1  (antizyme inhibitor 1)


Additional Information