Protein Disulfide Isomerase expression increases in resistance arteries during hypertension development. Effects on Nox 1 NADPH oxidase signaling
NADPH oxidases derived reactive oxygen species (ROS) play an important role in vascular function and remodeling in hypertension through redox signaling processes. Previous studies demonstrated that protein disulfide isomerase (PDI) regulates Nox1 expression and ROS generation in cultured vascular sm...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-03-01
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| Series: | Frontiers in Chemistry |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fchem.2015.00024/full |
| _version_ | 1819044336017342464 |
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| author | Aline Cristiane Depoli Androwiki Lívia de Lucca Camargo Simone Sartoretto Gisele Kruger Couto Izabela Martina Ramos Ribeiro Sidney Verissimo-Filho Luciana Venturini Rossoni Lucia Rossetti Lopes |
| author_facet | Aline Cristiane Depoli Androwiki Lívia de Lucca Camargo Simone Sartoretto Gisele Kruger Couto Izabela Martina Ramos Ribeiro Sidney Verissimo-Filho Luciana Venturini Rossoni Lucia Rossetti Lopes |
| author_sort | Aline Cristiane Depoli Androwiki |
| collection | DOAJ |
| description | NADPH oxidases derived reactive oxygen species (ROS) play an important role in vascular function and remodeling in hypertension through redox signaling processes. Previous studies demonstrated that protein disulfide isomerase (PDI) regulates Nox1 expression and ROS generation in cultured vascular smooth muscle cells. However, the role of PDI in conductance and resistance arteries during hypertension development remains unknown. The aim of the present study was to investigate PDI expression and NADPH oxidase dependent ROS generation during hypertension development. Mesenteric resistance arteries (MRA) and thoracic aorta were isolated from 6, 8 and 12 week-old spontaneously hypertensive (SHR) and Wistar rats. ROS production (dihydroethidium fluorescence), PDI (WB, imunofluorescence), Nox1 and NOX4 (RT-PCR) expression were evaluated. Results show a progressive increase in ROS generation in MRA and aorta from 8 to 12 week-old SHR. This effect was associated with a concomitant increase in PDI and Nox1 expression only in MRA. Therefore, suggesting a positive correlation between PDI and Nox1 expression during the development of hypertension in MRA. In order to investigate if this effect was due to an increase in arterial blood pressure, pre hypertensive SHR were treated with losartan (20mg/kg/day for 30 days), an AT1 receptor antagonist. Losartan decreased blood pressure and ROS generation in both vascular beds. However, only in SHR MRA losartan treatment lowered PDI and Nox1 expression to control levels. In MRA PDI inhibition (bacitracin, 0.5 mM) decreased Ang II redox signaling (p-ERK 1/2). Altogether, our results suggest that PDI plays a role in triggering oxidative stress and vascular dysfunction in resistance but not in conductance arteries, increasing Nox1 expression and activity. Therefore, PDI could be a new player in oxidative stress and functional alterations in resistance arteries during the establishment of hypertension. |
| first_indexed | 2024-12-21T10:11:03Z |
| format | Article |
| id | doaj.art-f868b31442b346708f46222f759f8b8f |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-21T10:11:03Z |
| publishDate | 2015-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-f868b31442b346708f46222f759f8b8f2022-12-21T19:07:43ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462015-03-01310.3389/fchem.2015.00024124740Protein Disulfide Isomerase expression increases in resistance arteries during hypertension development. Effects on Nox 1 NADPH oxidase signalingAline Cristiane Depoli Androwiki0Lívia de Lucca Camargo1Simone Sartoretto2Gisele Kruger Couto3Izabela Martina Ramos Ribeiro4Sidney Verissimo-Filho5Luciana Venturini Rossoni6Lucia Rossetti Lopes7University of São PauloUniversity of São PauloUniversity of São PauloUniversity of São PauloUniversity of São PauloUniversity of São PauloUniversity of São PauloUniversity of São PauloNADPH oxidases derived reactive oxygen species (ROS) play an important role in vascular function and remodeling in hypertension through redox signaling processes. Previous studies demonstrated that protein disulfide isomerase (PDI) regulates Nox1 expression and ROS generation in cultured vascular smooth muscle cells. However, the role of PDI in conductance and resistance arteries during hypertension development remains unknown. The aim of the present study was to investigate PDI expression and NADPH oxidase dependent ROS generation during hypertension development. Mesenteric resistance arteries (MRA) and thoracic aorta were isolated from 6, 8 and 12 week-old spontaneously hypertensive (SHR) and Wistar rats. ROS production (dihydroethidium fluorescence), PDI (WB, imunofluorescence), Nox1 and NOX4 (RT-PCR) expression were evaluated. Results show a progressive increase in ROS generation in MRA and aorta from 8 to 12 week-old SHR. This effect was associated with a concomitant increase in PDI and Nox1 expression only in MRA. Therefore, suggesting a positive correlation between PDI and Nox1 expression during the development of hypertension in MRA. In order to investigate if this effect was due to an increase in arterial blood pressure, pre hypertensive SHR were treated with losartan (20mg/kg/day for 30 days), an AT1 receptor antagonist. Losartan decreased blood pressure and ROS generation in both vascular beds. However, only in SHR MRA losartan treatment lowered PDI and Nox1 expression to control levels. In MRA PDI inhibition (bacitracin, 0.5 mM) decreased Ang II redox signaling (p-ERK 1/2). Altogether, our results suggest that PDI plays a role in triggering oxidative stress and vascular dysfunction in resistance but not in conductance arteries, increasing Nox1 expression and activity. Therefore, PDI could be a new player in oxidative stress and functional alterations in resistance arteries during the establishment of hypertension.http://journal.frontiersin.org/Journal/10.3389/fchem.2015.00024/fullAortaHypertensionNADPH OxidaseReactive Oxygen Speciesprotein disulfide isomeraseNox 1 |
| spellingShingle | Aline Cristiane Depoli Androwiki Lívia de Lucca Camargo Simone Sartoretto Gisele Kruger Couto Izabela Martina Ramos Ribeiro Sidney Verissimo-Filho Luciana Venturini Rossoni Lucia Rossetti Lopes Protein Disulfide Isomerase expression increases in resistance arteries during hypertension development. Effects on Nox 1 NADPH oxidase signaling Frontiers in Chemistry Aorta Hypertension NADPH Oxidase Reactive Oxygen Species protein disulfide isomerase Nox 1 |
| title | Protein Disulfide Isomerase expression increases in resistance arteries during hypertension development. Effects on Nox 1 NADPH oxidase signaling |
| title_full | Protein Disulfide Isomerase expression increases in resistance arteries during hypertension development. Effects on Nox 1 NADPH oxidase signaling |
| title_fullStr | Protein Disulfide Isomerase expression increases in resistance arteries during hypertension development. Effects on Nox 1 NADPH oxidase signaling |
| title_full_unstemmed | Protein Disulfide Isomerase expression increases in resistance arteries during hypertension development. Effects on Nox 1 NADPH oxidase signaling |
| title_short | Protein Disulfide Isomerase expression increases in resistance arteries during hypertension development. Effects on Nox 1 NADPH oxidase signaling |
| title_sort | protein disulfide isomerase expression increases in resistance arteries during hypertension development effects on nox 1 nadph oxidase signaling |
| topic | Aorta Hypertension NADPH Oxidase Reactive Oxygen Species protein disulfide isomerase Nox 1 |
| url | http://journal.frontiersin.org/Journal/10.3389/fchem.2015.00024/full |
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