Role of Nrf2 and protective effects of Metformin against tobacco smoke-induced cerebrovascular toxicity
Cigarette smoking (CS) is associated with vascular endothelial dysfunction in a causative way primarily related to the TS content of reactive oxygen species (ROS), nicotine, and inflammation. TS promotes glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM) with whi...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-08-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231717300484 |
| _version_ | 1819060627538182144 |
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| author | Shikha Prasad Ravi K. Sajja Mohammad Abul Kaisar Jee Hyun Park Heidi Villalba Taylor Liles Thomas Abbruscato Luca Cucullo |
| author_facet | Shikha Prasad Ravi K. Sajja Mohammad Abul Kaisar Jee Hyun Park Heidi Villalba Taylor Liles Thomas Abbruscato Luca Cucullo |
| author_sort | Shikha Prasad |
| collection | DOAJ |
| description | Cigarette smoking (CS) is associated with vascular endothelial dysfunction in a causative way primarily related to the TS content of reactive oxygen species (ROS), nicotine, and inflammation. TS promotes glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM) with which it shares other pathogenic traits including the high risk of cerebrovascular and neurological disorders like stroke via ROS generation, inflammation, and blood-brain barrier (BBB) impairment. Herein we provide evidence of the role played by nuclear factor erythroid 2-related factor (Nrf2) in CS-induced cerebrobvascular/BBB impairments and how these cerebrovascular harmful effects can be circumvented by the use of metformin (MF; a widely prescribed, firstline anti-diabetic drug) treatment. Our data in fact revealed that MF activates counteractive mechanisms primarily associated with the Nrf2 pathway which drastically reduce CS toxicity at the cerebrovascular level. These include the suppression of tight junction (TJ) protein downregulation and loss of BBB integrity induced by CS, reduction of inflammation and oxidative stress, renormalization of the expression levels of the major BBB glucose transporter Glut-1 and that of the anticoagulant factor thrombomodulin. Further, we provide additional insights on the controversial interplay between Nrf2 and AMPK. Keywords: Oxidative stress, Cigarette smoke, Metformin, Blood hemostasis, Blood brain barrier, Tight junctions, Nrf2, Glucose transporter |
| first_indexed | 2024-12-21T14:30:00Z |
| format | Article |
| id | doaj.art-4703dbec5c76403b8657c93f59e81775 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-21T14:30:00Z |
| publishDate | 2017-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-4703dbec5c76403b8657c93f59e817752022-12-21T19:00:32ZengElsevierRedox Biology2213-23172017-08-01125869Role of Nrf2 and protective effects of Metformin against tobacco smoke-induced cerebrovascular toxicityShikha Prasad0Ravi K. Sajja1Mohammad Abul Kaisar2Jee Hyun Park3Heidi Villalba4Taylor Liles5Thomas Abbruscato6Luca Cucullo7Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 S. Coulter Street, Amarillo, TX 79106, USADepartment of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 S. Coulter Street, Amarillo, TX 79106, USADepartment of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 S. Coulter Street, Amarillo, TX 79106, USADepartment of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 S. Coulter Street, Amarillo, TX 79106, USADepartment of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 S. Coulter Street, Amarillo, TX 79106, USADepartment of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 S. Coulter Street, Amarillo, TX 79106, USADepartment of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 S. Coulter Street, Amarillo, TX 79106, USA; Center for Blood Brain Barrier Research, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USADepartment of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 S. Coulter Street, Amarillo, TX 79106, USA; Center for Blood Brain Barrier Research, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA; Corresponding author at: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 S. Coulter Street, Amarillo, TX 79106, USA.Cigarette smoking (CS) is associated with vascular endothelial dysfunction in a causative way primarily related to the TS content of reactive oxygen species (ROS), nicotine, and inflammation. TS promotes glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM) with which it shares other pathogenic traits including the high risk of cerebrovascular and neurological disorders like stroke via ROS generation, inflammation, and blood-brain barrier (BBB) impairment. Herein we provide evidence of the role played by nuclear factor erythroid 2-related factor (Nrf2) in CS-induced cerebrobvascular/BBB impairments and how these cerebrovascular harmful effects can be circumvented by the use of metformin (MF; a widely prescribed, firstline anti-diabetic drug) treatment. Our data in fact revealed that MF activates counteractive mechanisms primarily associated with the Nrf2 pathway which drastically reduce CS toxicity at the cerebrovascular level. These include the suppression of tight junction (TJ) protein downregulation and loss of BBB integrity induced by CS, reduction of inflammation and oxidative stress, renormalization of the expression levels of the major BBB glucose transporter Glut-1 and that of the anticoagulant factor thrombomodulin. Further, we provide additional insights on the controversial interplay between Nrf2 and AMPK. Keywords: Oxidative stress, Cigarette smoke, Metformin, Blood hemostasis, Blood brain barrier, Tight junctions, Nrf2, Glucose transporterhttp://www.sciencedirect.com/science/article/pii/S2213231717300484 |
| spellingShingle | Shikha Prasad Ravi K. Sajja Mohammad Abul Kaisar Jee Hyun Park Heidi Villalba Taylor Liles Thomas Abbruscato Luca Cucullo Role of Nrf2 and protective effects of Metformin against tobacco smoke-induced cerebrovascular toxicity Redox Biology |
| title | Role of Nrf2 and protective effects of Metformin against tobacco smoke-induced cerebrovascular toxicity |
| title_full | Role of Nrf2 and protective effects of Metformin against tobacco smoke-induced cerebrovascular toxicity |
| title_fullStr | Role of Nrf2 and protective effects of Metformin against tobacco smoke-induced cerebrovascular toxicity |
| title_full_unstemmed | Role of Nrf2 and protective effects of Metformin against tobacco smoke-induced cerebrovascular toxicity |
| title_short | Role of Nrf2 and protective effects of Metformin against tobacco smoke-induced cerebrovascular toxicity |
| title_sort | role of nrf2 and protective effects of metformin against tobacco smoke induced cerebrovascular toxicity |
| url | http://www.sciencedirect.com/science/article/pii/S2213231717300484 |
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