Over-expressed copper/zinc superoxide dismutase localizes to mitochondria in neurons inhibiting the angiotensin II-mediated increase in mitochondrial superoxide
| العنوان: | Over-expressed copper/zinc superoxide dismutase localizes to mitochondria in neurons inhibiting the angiotensin II-mediated increase in mitochondrial superoxide |
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| المؤلفون: | Matthew C. Zimmerman, Adam J. Case, Harold D. Schultz, Shumin Li, Rui-Fang Yang |
| المصدر: | Redox Biology, Vol 2, Iss C, Pp 8-14 (2014) Redox Biology |
| بيانات النشر: | The Authors. Published by Elsevier B.V. |
| مصطلحات موضوعية: | Patch-Clamp Techniques, Clinical Biochemistry, 030204 cardiovascular system & hematology, Mitochondrion, Biochemistry, Mice, chemistry.chemical_compound, 0302 clinical medicine, Superoxides, lcsh:QH301-705.5, chemistry.chemical_classification, Neurons, 0303 health sciences, lcsh:R5-920, NADPH oxidase, biology, Superoxide, AngII, angiotensin II, Angiotensin II, Neurogenic hypertension, NOX, NADPH oxidase, 3. Good health, Cell biology, Mitochondria, cardiovascular system, MIMS, mitochondrial inter-membrane space, Signal transduction, CuZnSOD, lcsh:Medicine (General), CuZnSOD, copper/zinc superoxide dismutase, hormones, hormone substitutes, and hormone antagonists, Signal Transduction, Research Paper, Genetic Vectors, Adenoviridae, Cell Line, Ikv, neuronal potassium current, Superoxide dismutase, 03 medical and health sciences, ROS, reactive oxygen species, RAS, renin–angiotensin system, Animals, MnSOD, manganese superoxide dismutase, 030304 developmental biology, Reactive oxygen species, Superoxide Dismutase, Organic Chemistry, Potassium current, chemistry, lcsh:Biology (General), AT1R, angiotensin type 1 receptor, biology.protein |
| الوصف: | Angiotensin II (AngII) is the main effector peptide of the renin–angiotensin system (RAS), and contributes to the pathogenesis of cardiovascular disease by exerting its effects on an array of different cell types, including central neurons. AngII intra-neuronal signaling is mediated, at least in part, by reactive oxygen species, particularly superoxide (O2•−). Recently, it has been discovered that mitochondria are a major subcellular source of AngII-induced O2•−. We have previously reported that over-expression of manganese superoxide dismutase (MnSOD), a mitochondrial matrix-localized O2•− scavenging enzyme, inhibits AngII intra-neuronal signaling. Interestingly, over-expression of copper/zinc superoxide dismutase (CuZnSOD), which is believed to be primarily localized to the cytoplasm, similarly inhibits AngII intra-neuronal signaling and provides protection against AngII-mediated neurogenic hypertension. Herein, we tested the hypothesis that CuZnSOD over-expression in central neurons localizes to mitochondria and inhibits AngII intra-neuronal signaling by scavenging mitochondrial O2•−. Using a neuronal cell culture model (CATH.a neurons), we demonstrate that both endogenous and adenovirus-mediated over-expressed CuZnSOD (AdCuZnSOD) are present in mitochondria. Furthermore, we show that over-expression of CuZnSOD attenuates the AngII-mediated increase in mitochondrial O2•− levels and the AngII-induced inhibition of neuronal potassium current. Taken together, these data clearly show that over-expressed CuZnSOD in neurons localizes in mitochondria, scavenges AngII-induced mitochondrial O2•−, and inhibits AngII intra-neuronal signaling. Graphical abstract Highlights • Endogenous CuZnSOD is localized to mitochondria of AngII-sensitive neurons. • Adenovirus-mediated over-expressed CuZnSOD is localized to neuron mitochondria. • AngII-induced mitochondrial O2•− flux is attenuated by CuZnSOD over-expression. • Over-expressed CuZnSOD reduces AngII-mediated inhibition of neuronal K+ current. |
| اللغة: | English |
| تدمد: | 2213-2317 |
| DOI: | 10.1016/j.redox.2013.11.002 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ede80d92672c3cee642c9cf874febfb8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ede80d92672c3cee642c9cf874febfb8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22132317 |
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| DOI: | 10.1016/j.redox.2013.11.002 |