| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Sauler, Maor Shan, Peiying Lee, Patty J. Gong, Huan Haslip, Maria Shinn, Amanda S. Zhang, Yi Mannam, Praveen |
| Description |
Author Affiliation: Zhang Y ( Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine, New Haven, CT 06520.); Sauler M ( Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine, New Haven, CT 06520.); Shinn AS ( Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine, New Haven, CT 06520.); Gong H ( Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine, New Haven, CT 06520.); Haslip M ( Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine, New Haven, CT 06520.); Shan P ( Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine, New Haven, CT 06520.); Mannam P ( Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine, New Haven, CT 06520.); Lee PJ ( Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine, New Haven, CT 06520 patty.lee@yale.edu.) |
| Abstract |
High levels of inspired oxygen, hyperoxia, are frequently used in patients with acute respiratory failure. Hyperoxia can exacerbate acute respiratory failure, which has high mortality and no specific therapies. We identified novel roles for PTEN-induced putative kinase 1 (PINK1), a mitochondrial protein, and the cytosolic innate immune protein NLRP3 in the lung and endothelium. We generated double knockouts (PINK1(-/-)/NLRP3(-/-)), as well as cell-targeted PINK1 silencing and lung-targeted overexpression constructs, to specifically show that PINK1 mediates cytoprotection in wild-type and NLRP3(-/-) mice. The ability to resist hyperoxia is proportional to PINK1 expression. PINK1(-/-) mice were the most susceptible; wild-type mice, which induced PINK1 after hyperoxia, had intermediate susceptibility; and NLRP3(-/-) mice, which had high basal and hyperoxia-induced PINK1, were the least susceptible. Genetic deletion of PINK1 or PINK1 silencing in the lung endothelium increased susceptibility to hyperoxia via alterations in autophagy/mitophagy, proteasome activation, apoptosis, and oxidant generation. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1400653 |
| Journal |
The Journal of Immunology |
| Issue Number |
11 |
| Volume Number |
192 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2014-06-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Carrier Proteins Immunology Endothelium Hyperoxia Lung Oxidants Adverse Effects Protein Kinases Animals Genetics Pathology Enzyme Induction Drug Effects Prevention & Control Mice Mice, Knockout Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
