Heme oxygenase (HO) catalyzes the first and rate limiting step in the degradation of heme to yield equimolar quantities of biliverdin Ixa, carbon monoxide (CO), and iron. HO-1, the inducible isoform, is highly induced by a variety of causing oxidative stress including hydrogen peroxide, glutathione depletors, UV irradiation, endotoxin, and hyperoxia. This diversity of HO-1 inducers has provided further support for the speculation that HO-1, besides its role in heme degradation, may also play a vital function in maintaining cellular homeostasis. Our laboratory and others have demonstrated that induction of HO-1 provides protection both in vivo and in vitro against oxidation stress including hyperoxia. The mechanism(s) by which HO-1 provides protection against oxidative stress is poorly understood. Our recent studies (see Progress Report/Preliminary Studies) highlight the formal possibility that the gaseous molecule CO can mediate the protective effects of HO-1 against oxidant-induced lung injury principally via its anti-inflammatory and anti-apoptotic properties. We therefore hypothesize that CO mediates HO-1 induced cytoprotection against hyperoxic lung injury. Furthermore, we hypothesize that CO mediates the cytoprotection via the p38 mitogen activated protein kinase (MAPK) signaling pathway.
| Ma, Kevin C; Schenck, Edward J; Pabon, Maria A et al. (2018) The Role of Danger Signals in the Pathogenesis and Perpetuation of Critical Illness. Am J Respir Crit Care Med 197:300-309 |
| Schenck, Edward J; Oromendia, Clara; Torres, Lisa K et al. (2018) Rapidly Improving ARDS in Therapeutic Randomized Controlled Trials. Chest : |
| Schenck, Edward J; Ma, Kevin C; Murthy, Santosh B et al. (2018) Danger Signals in the ICU. Crit Care Med 46:791-798 |
| Ryter, Stefan W; Ma, Kevin C; Choi, Augustine M K (2018) Carbon monoxide in lung cell physiology and disease. Am J Physiol Cell Physiol 314:C211-C227 |
| Harrington, John S; Schenck, Edward J; Oromendia, Clara et al. (2018) Acute respiratory distress syndrome without identifiable risk factors: A secondary analysis of the ARDS network trials. J Crit Care 47:49-54 |
| Siempos, Ilias I; Ma, Kevin C; Imamura, Mitsuru et al. (2018) RIPK3 mediates pathogenesis of experimental ventilator-induced lung injury. JCI Insight 3: |
| Lee, Seonmin; Nakahira, Kiichi; Dalli, Jesmond et al. (2017) NLRP3 Inflammasome Deficiency Protects against Microbial Sepsis via Increased Lipoxin B4 Synthesis. Am J Respir Crit Care Med 196:713-726 |
| Finkelsztein, Eli J; Jones, Daniel S; Ma, Kevin C et al. (2017) Comparison of qSOFA and SIRS for predicting adverse outcomes of patients with suspicion of sepsis outside the intensive care unit. Crit Care 21:73 |
| Zhang, Ruoyu; Nakahira, Kiichi; Guo, Xiaoxian et al. (2016) Very Short Mitochondrial DNA Fragments and Heteroplasmy in Human Plasma. Sci Rep 6:36097 |
| Ryter, Stefan W; Choi, Augustine M K (2016) Targeting heme oxygenase-1 and carbon monoxide for therapeutic modulation of inflammation. Transl Res 167:7-34 |
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