Expression Level and Subcellular Localization of Heme Oxygenase-1 Modulates Its Cytoprotective Properties in Response to Lung Injury: A Mouse Model

• DOI: 10.1371/journal.pone.0090936
• Publication Date: 2014-03-05T21:48:06Z
• Authors: Fumihiko Namba; Hayato Go; Jennifer A. Murphy; Ping La; Guang Yang; Shaon Sengupta; Amal P. Fernando; Mekdes Yohannes; Chhanda Biswas; Suzanne L. Wehrli; Phyllis A. Dennery
• Keywords: Hyperoxia

Premature infants exposed to hyperoxia suffer acute and long-term pulmonary consequences. Nevertheless, neonates survive better than adults. The factors contributing neonatal hyperoxic tolerance are not fully elucidated. In contrast adults, heme oxygenase (HO)-1, an endoplasmic reticulum (ER)-anchored protein, is abundant in the lung but inducible response hyperoxia. latter may be important, because very high levels of HO-1 overexpression associated with significant oxygen cytotoxicity vitro. Also, localizes nucleus mice To understand mechanisms by which expression subcellular localization contribute neonates, lung-specific transgenic expressing or low full-length (cytoplasmic, HO-1-FL(H) HO-1-FL(L)) C-terminally truncated (nuclear, Nuc-HO-1-TR) were generated. HO-1-FL(L), lungs had a normal alveolar appearance lesser oxidative damage after exposure. contrast, HO-1-FL(H), wall thickness type II cell hyperproliferation was observed as well worsened function evidence abnormal recovery from Nuc-HO-1-TR, increased DNA damage, poly (ADP-ribose) polymerase (PARP) protein expression, reduced (PAR) hydrolysis These data indicate that cytoplasmic protect against hyperoxia-induced injury attenuating stress, whereas worsen increasing proliferation decreasing apoptosis cells. Enhanced nuclear impaired disabling PAR-dependent regulation repair. Lastly both predisposed cellular proliferation. maximize cytoprotective effects, therapeutic strategies must account for specific effects its levels.