Dysregulation of CLOCK gene expression in hyperoxia-induced lung injury.
نویسندگان
چکیده
Hyperoxic acute lung injury (HALI) is characterized by inflammation and epithelial cell death. CLOCK genes are master regulators of circadian rhythm also implicated in inflammation and lung diseases. However, the relationship of CLOCK genes in hyperoxia-induced lung injury has not been studied. This study will determine if HALI alters CLOCK gene expression. To test this, wild-type and NALP3(-/-) mice were exposed to room air or hyperoxia for 24, 48, or 72 h. In addition, mice were exposed to different concentrations of hyperoxia (50, 75, or 100% O2) or room air for 72 h. The mRNA and protein levels of lung CLOCK genes, based on quantitative PCR and Western blot analysis, respectively, and their target genes are significantly elevated in mice exposed to hyperoxia compared with controls. Alterations in CLOCK genes are associated with increased inflammatory markers in bronchoalveolar lavage fluid of hyperoxic mice compared with controls. Histological examination of mice lungs exposed to hyperoxia show increased inflammation and alveolar congestion compared with controls. Our results indicate sequential increase in CLOCK gene expression in lungs of mice exposed to hyperoxia compared with controls. Additionally, data suggest a dose-dependent increase in CLOCK gene expression with increased oxygen concentrations. To validate if the expression changes related to CLOCK genes are indeed associated with inflammation, NALP3(-/-) was introduced to analyze loss of function in inflammation. Western blot analysis showed significant CLOCK gene downregulation in NALP3(-/-) mice compared with wild-type controls. Together, our results demonstrate that hyperoxia-mediated lung inflammation is associated with alterations in CLOCK gene expression.
منابع مشابه
CALL FOR PAPERS Cellular Circadian Rhythms Dysregulation of CLOCK gene expression in hyperoxia-induced lung injury
Lagishetty V, Parthasarathy PT, Phillips O, Fukumoto J, Cho Y, Fukumoto I, Bao H, Cox R Jr, Galam L, Lockey RF, Kolliputi N. Dysregulation of CLOCK gene expression in hyperoxia-induced lung injury. Am J Physiol Cell Physiol 306: C999–C1007, 2014. First published April 2, 2014; doi:10.1152/ajpcell.00064.2013.—Hyperoxic acute lung injury (HALI) is characterized by inflammation and epithelial cell...
متن کاملTime course changes of oxidative stress and inflammation in hyperoxia-induced acute lung injury in rats
Objective(s):Therapies with high levels of oxygen are commonly used in the management of critical care. However, prolonged exposure to hyperoxia can cause acute lung injury. Although oxidative stress and inflammation are purported to play an important role in the pathogenesis of acute lung injury, the exact mechanisms are still less known in the hyperoxic acute lung injury (HALI). Materials ...
متن کاملRetracted: Time course changes of oxidative stress and inflammation in hyperoxia-induced acute lung injury in rats
متن کامل
Asiaticoside attenuates hyperoxia-induced lung injury in vitro andin vivo
Objective(s): Asiaticoside (AS) displays anti-inflammation, and anti-apoptosis effect, but the role of AS in hyperoxia-induced lung injury (HILI) treatment is undefined. Therefore, the aim of this study was to investigate the effects of AS on HILI on premature rats and alveolar type II (AEC II) cells.Materials and Methods: Sprague-Dawley...
متن کاملLow-molecular-weight heparin reduces hyperoxia-augmented ventilator-induced lung injury via serine/threonine kinase-protein kinase B
BACKGROUND High-tidal-volume mechanical ventilation and hyperoxia used in patients with acute lung injury (ALI) can induce the release of cytokines, including high-mobility group box-1 (HMGB1), oxygen radicals, neutrophil infiltration, and the disruption of epithelial and endothelial barriers. Hyperoxia has been shown to increase ventilator-induced lung injury, but the mechanisms regulating int...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- American journal of physiology. Cell physiology
دوره 306 11 شماره
صفحات -
تاریخ انتشار 2014