system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, RESULTS. Meshes: Adenosine Triphosphate, Angiotensin II, Animals, Antioxidants, Blood Pressure, Blood Vessels, Catalase, Cell Respiration, Cyclic N-Oxides, Disease Models, Animal, Enzyme Inhibitors, Homeostasis, Humans, Hydrogen Peroxide, Hypertension, Imidazoles, Ion Channels, Male, Medulla Oblongata, Microinjections, Mitochondria, Mitochondrial Proteins, NADPH Oxidases, Onium Compounds, Oxidative Stress, PPAR gamma, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Phosphorylation, Pyridines, RNA-Binding Proteins, Rats, Rats, Sprague-Dawley, Rosiglitazone, Spin Labels, Superoxide Dismutase, Superoxide Dismutase-1, Superoxides, Sympathetic Nervous System, Thiazolidinediones, Time Factors, Transcription Factors, Transcriptional Activation, Transduction, Genetic, Uncoupling Protein 2, Up-Regulation, p38 Mitogen-Activated Protein Kinases.
user
Does transcriptional upregulation of mitochondrial uncoupling protein 2 protect against oxidative stress-associated neurogenic hypertension? Context: Mitochondrial uncoupling proteins (UCPs) belong to a superfamily of mitochondrial anion transporters that uncouple ATP synthesis from oxidative phosphorylation and mitigates mitochondrial reactive oxygen species production. We assessed the hypothesis that UCP2 participates in central cardiovascular regulation by maintaining reactive oxygen species homeostasis in the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons that maintain vasomotor tone located. We also elucidated the molecular mechanisms that underlie transcriptional upregulation of UCP2 in response to oxidative stress in RVLM. In Sprague-Dawley rats, transcriptional upregulation of UCP2 in RVLM by rosiglitazone, an activator of its transcription factor peroxisome proliferator-activated receptor (PPAR)gamma, reduced mitochondrial hydrogen peroxide level in RVLM and systemic arterial pressure. Oxidative stress induced by microinjection of angiotensin II into RVLM augmented UCP2 mRNA or protein expression in RVLM, which was antagonized by comicroinjection of NADPH oxidase inhibitor (diphenyleneiodonium chloride), superoxide dismutase mimetic (tempol), or p38 mitogen-activated protein kinase inhibitor (SB203580) but not by extracellular signal-regulated kinase 1/2 inhibitor (U0126). Angiotensin II also induced phosphorylation of the PPARgamma coactivator, PPARgamma coactivator (PGC)-1alpha, and an increase in formation of PGC-1alpha/PPARgamma complexes in a p38 mitogen-activated protein kinase-dependent manner. Intracerebroventricular infusion of angiotensin II promoted an increase in mitochondrial hydrogen peroxide production in RVLM and chronic pressor response, which was potentiated by gene knockdown of UCP2 but blunted by rosiglitazone.
assistant
These results suggest that transcriptional upregulation of mitochondrial UCP2 in response to an elevation in superoxide plays an active role in feedback regulation of reactive oxygen species production in RVLM and neurogenic hypertension associated with chronic oxidative stress. Final Decision: yes