Heme Oxygenase-2 Localizes to Mitochondria and Regulates Hypoxic Responses in Hepatocytes
| Autor: | Mitch Dyer, Brian S. Zuckerbraun, Jason L. Sperry, Matthew R. Rosengart, Patricia Loughran, Benjamin Kautza, Paul Waltz, Donna B. Stolz, Jason Luciano, Matthew D. Neal |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Mitochondrial ROS Aging Cell signaling Article Subject MAP Kinase Signaling System Cell Mitochondria Liver Shock Hemorrhagic Mitochondrion Biochemistry Mice 03 medical and health sciences Oxygen Consumption 0302 clinical medicine medicine Animals lcsh:QH573-671 chemistry.chemical_classification Gene knockdown Reactive oxygen species lcsh:Cytology Cell Biology General Medicine Hypoxia (medical) Hypoxia-Inducible Factor 1 alpha Subunit Cell Hypoxia Cell biology Mice Inbred C57BL Oxygen Heme oxygenase 030104 developmental biology medicine.anatomical_structure chemistry Gene Knockdown Techniques Heme Oxygenase (Decyclizing) Hepatocytes medicine.symptom 030217 neurology & neurosurgery Research Article |
| Zdroj: | Oxidative Medicine and Cellular Longevity, Vol 2018 (2018) Oxidative Medicine and Cellular Longevity |
| ISSN: | 1942-0994 1942-0900 |
| Popis: | Hypoxia occurs as a part of multiple disease states, including hemorrhagic shock. Adaptive responses occur within the cell to limit the consequences of hypoxia. This includes changes in mitochondrial respiration, stress-induced cell signaling, and gene expression that is regulated by hypoxia inducible factor-1α(HIF-1α). Heme oxygenase-2 (HO-2) has been shown to be involved in oxygen sensing in several cell types. The purpose of these experiments was to test the hypothesis that HO-2 is a critical regulator of mitochondrial oxygen consumption and reactive oxygen species (ROS) production to influence hypoxia-adaptive responses such as HIF-1αprotein levels and JNK signaling.Methods and Results.In vitrostudies were performed in primary mouse hepatocytes. HO-2, but not HO-1, was expressed in mitochondria at baseline. Decreased oxygen consumption and increased mitochondrial ROS production in response to hypoxia were dependent upon HO-2 expression. HO-2 expression regulated HIF-1αand JNK signaling in a mitochondrial ROS-dependent manner. Furthermore, knockdown of HO-2 led to increased organ damage, systemic inflammation, tissue hypoxia, and shock in a murine model of hemorrhage and resuscitation.Conclusion. HO-2 signaling plays a role in hypoxic signaling and hemorrhagic shock. This pathway may be able to be harnessed for therapeutic effects. |
| Databáze: | OpenAIRE |
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