Over-expressed copper/zinc superoxide dismutase localizes to mitochondria in neurons inhibiting the angiotensin II-mediated increase in mitochondrial superoxide
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.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2013 |
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Erschienen: |
2013 |
Enthalten in: |
Zur Gesamtaufnahme - volume:2 |
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Enthalten in: |
Redox biology - 2(2013) vom: 15., Seite 8-14 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Li, Shumin [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 30.03.2015 Date Revised 21.10.2021 published: Electronic-eCollection Citation Status MEDLINE |
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doi: |
10.1016/j.redox.2013.11.002 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM233905707 |
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100 | 1 | |a Li, Shumin |e verfasserin |4 aut | |
245 | 1 | 0 | |a Over-expressed copper/zinc superoxide dismutase localizes to mitochondria in neurons inhibiting the angiotensin II-mediated increase in mitochondrial superoxide |
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520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a AT1R, angiotensin type 1 receptor | |
650 | 4 | |a AngII, angiotensin II | |
650 | 4 | |a Angiotensin II | |
650 | 4 | |a CuZnSOD | |
650 | 4 | |a CuZnSOD, copper/zinc superoxide dismutase | |
650 | 4 | |a Ikv, neuronal potassium current | |
650 | 4 | |a MIMS, mitochondrial inter-membrane space | |
650 | 4 | |a Mitochondria | |
650 | 4 | |a MnSOD, manganese superoxide dismutase | |
650 | 4 | |a NOX, NADPH oxidase | |
650 | 4 | |a Neurons | |
650 | 4 | |a Potassium current | |
650 | 4 | |a RAS, renin–angiotensin system | |
650 | 4 | |a ROS, reactive oxygen species | |
650 | 4 | |a Superoxide | |
650 | 7 | |a Superoxides |2 NLM | |
650 | 7 | |a 11062-77-4 |2 NLM | |
650 | 7 | |a Angiotensin II |2 NLM | |
650 | 7 | |a 11128-99-7 |2 NLM | |
650 | 7 | |a Superoxide Dismutase |2 NLM | |
650 | 7 | |a EC 1.15.1.1 |2 NLM | |
700 | 1 | |a Case, Adam J |e verfasserin |4 aut | |
700 | 1 | |a Yang, Rui-Fang |e verfasserin |4 aut | |
700 | 1 | |a Schultz, Harold D |e verfasserin |4 aut | |
700 | 1 | |a Zimmerman, Matthew C |e verfasserin |4 aut | |
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