| First Author | Jin Y | Year | 2019 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 316 |
| Issue | 4 | Pages | L598-L607 |
| PubMed ID | 30628488 | Mgi Jnum | J:273118 |
| Mgi Id | MGI:6283794 | Doi | 10.1152/ajplung.00223.2018 |
| Citation | Jin Y, et al. (2019) Deficiency of cationic amino acid transporter-2 protects mice from hyperoxia-induced lung injury. Am J Physiol Lung Cell Mol Physiol 316(4):L598-L607 |
| abstractText | The pathology of acute lung injury (ALI) involves inducible nitric oxide (NO) synthase (iNOS)-derived NO-induced apoptosis of pulmonary endothelial cells. In vitro, iNOS-derived NO production has been shown to depend on the uptake of l-arginine by the cationic amino acid transporters (CAT). To test the hypothesis that mice deficient in CAT-2 ( slc7a2(-/-) on a C57BL/6 background) would be protected from hyperoxia-induced ALI, mice ( slc7a2(-/-) or wild-type) were placed in >95% oxygen (hyperoxia) or 21% oxygen (control) for 60 h. In wild-type mice exposed to hyperoxia, the exhaled nitric oxide (exNO) was twofold greater than in wild-type mice exposed to normoxia ( P < 0.005), whereas in slc7a2(-/-) mice there was no significant difference between exNO in animals exposed to hyperoxia or normoxia ( P = 0.95). Hyperoxia-exposed wild-type mice had greater ( P < 0.05) lung resistance and a lower ( P < 0.05) lung compliance than did hyperoxia-exposed slc7a2(-/-) mice. The lung wet-to-dry weight ratio was greater ( P < 0.005) in the hyperoxia-exposed wild-type mice than in hyperoxia-exposed slc7a2(-/-) mice. Neutrophil infiltration was lower ( P < 0.05) in the hyperoxia-exposed slc7a2(-/-) mice than in the hyperoxia-exposed wild-type mice as measured by myeloperoxidase activity. The protein concentration in bronchoalveolar lavage fluid was lower ( P < 0.001) in the hyperoxia-exposed slc7a2(-/-) mice than in similarly exposed wild-type mice. The percent of TUNEL-positive cells in the lung following hyperoxia exposure was significantly lower ( P < 0.001) in the slc7a2(-/-) mice than in the wild-type mice. These results are consistent with our hypothesis that lack of CAT-2 protects mice from acute lung injury. |
