Smoke Exposure Causes Endoplasmic Reticulum Stress and Lipid Accumulation in Retinal Pigment Epithelium through Oxidative Stress and Complement Activation.
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| Title: | Smoke Exposure Causes Endoplasmic Reticulum Stress and Lipid Accumulation in Retinal Pigment Epithelium through Oxidative Stress and Complement Activation. |
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| Authors: | Kunchithapautham, Kannan1, Atkinson, Carl2, Rohrer, Bärbel1,3 rohrer@musc.edu |
| Source: | Journal of Biological Chemistry. 5/23/2014, Vol. 289 Issue 21, p14534-14546. 13p. |
| Subjects: | Physiological effects of tobacco, Rhodopsin, Complement (Immunology), Cellular signal transduction, Endoplasmic reticulum, Oxidative stress, Retinal degeneration, Laboratory mice |
| Abstract: | Age-related macular degeneration (AMD) is a complex disease caused by genetic and environmental factors, including genetic variants in complement components and smoking. Smoke exposure leads to oxidative stress, complement activation, endoplasmic reticulum (ER) stress, and lipid dysregulation, which have all been proposed to be associated with AMD pathogenesis. Here we examine the effects of smoke exposure on the retinal pigment epithelium (RPE). Mice were exposed to cigarette smoke or filtered air for 6 months. RPE cells grown as stable monolayers were exposed to 5% cigarette smoke extract (CSE). Effects of smoke were determined by biochemical, molecular, and histological measures. Effects of the alternative pathway (AP) of complement and complement C3a anaphylatoxin receptor signaling were analyzed using knock-out mice or specific inhibitors. ER stress markers were elevated after smoke exposure in RPE of intact mice, which was eliminated in AP-deficient mice.To examine this relationship further, RPE monolayers were exposed to CSE. Short term smoke exposure resulted in production and release of complement C3, the generation of C3a, oxidative stress, complement activation on the cell membrane, and ER stress. Long term exposure to CSE resulted in lipid accumulation, and secretion. All measures were reversed by blocking C3a complement receptor (C3aR), alternative complement pathway signaling, and antioxidant therapy. Taken together, our results provide clear evidence that smoke exposure results in oxidative stress and complement activation via the AP, resulting in ER stress-mediated lipid accumulation, and further suggesting that oxidative stress and complement act synergistically in the pathogenesis of AMD. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 96278154 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Smoke Exposure Causes Endoplasmic Reticulum Stress and Lipid Accumulation in Retinal Pigment Epithelium through Oxidative Stress and Complement Activation. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Kunchithapautham%2C+Kannan%22">Kunchithapautham, Kannan</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Atkinson%2C+Carl%22">Atkinson, Carl</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Rohrer%2C+Bärbel%22">Rohrer, Bärbel</searchLink><relatesTo>1,3</relatesTo><i> rohrer@musc.edu</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 5/23/2014, Vol. 289 Issue 21, p14534-14546. 13p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Physiological+effects+of+tobacco%22">Physiological effects of tobacco</searchLink><br /><searchLink fieldCode="DE" term="%22Rhodopsin%22">Rhodopsin</searchLink><br /><searchLink fieldCode="DE" term="%22Complement+%28Immunology%29%22">Complement (Immunology)</searchLink><br /><searchLink fieldCode="DE" term="%22Cellular+signal+transduction%22">Cellular signal transduction</searchLink><br /><searchLink fieldCode="DE" term="%22Endoplasmic+reticulum%22">Endoplasmic reticulum</searchLink><br /><searchLink fieldCode="DE" term="%22Oxidative+stress%22">Oxidative stress</searchLink><br /><searchLink fieldCode="DE" term="%22Retinal+degeneration%22">Retinal degeneration</searchLink><br /><searchLink fieldCode="DE" term="%22Laboratory+mice%22">Laboratory mice</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Age-related macular degeneration (AMD) is a complex disease caused by genetic and environmental factors, including genetic variants in complement components and smoking. Smoke exposure leads to oxidative stress, complement activation, endoplasmic reticulum (ER) stress, and lipid dysregulation, which have all been proposed to be associated with AMD pathogenesis. Here we examine the effects of smoke exposure on the retinal pigment epithelium (RPE). Mice were exposed to cigarette smoke or filtered air for 6 months. RPE cells grown as stable monolayers were exposed to 5% cigarette smoke extract (CSE). Effects of smoke were determined by biochemical, molecular, and histological measures. Effects of the alternative pathway (AP) of complement and complement C3a anaphylatoxin receptor signaling were analyzed using knock-out mice or specific inhibitors. ER stress markers were elevated after smoke exposure in RPE of intact mice, which was eliminated in AP-deficient mice.To examine this relationship further, RPE monolayers were exposed to CSE. Short term smoke exposure resulted in production and release of complement C3, the generation of C3a, oxidative stress, complement activation on the cell membrane, and ER stress. Long term exposure to CSE resulted in lipid accumulation, and secretion. All measures were reversed by blocking C3a complement receptor (C3aR), alternative complement pathway signaling, and antioxidant therapy. Taken together, our results provide clear evidence that smoke exposure results in oxidative stress and complement activation via the AP, resulting in ER stress-mediated lipid accumulation, and further suggesting that oxidative stress and complement act synergistically in the pathogenesis of AMD. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1074/jbc.M114.564674 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 13 StartPage: 14534 Subjects: – SubjectFull: Physiological effects of tobacco Type: general – SubjectFull: Rhodopsin Type: general – SubjectFull: Complement (Immunology) Type: general – SubjectFull: Cellular signal transduction Type: general – SubjectFull: Endoplasmic reticulum Type: general – SubjectFull: Oxidative stress Type: general – SubjectFull: Retinal degeneration Type: general – SubjectFull: Laboratory mice Type: general Titles: – TitleFull: Smoke Exposure Causes Endoplasmic Reticulum Stress and Lipid Accumulation in Retinal Pigment Epithelium through Oxidative Stress and Complement Activation. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Kunchithapautham, Kannan – PersonEntity: Name: NameFull: Atkinson, Carl – PersonEntity: Name: NameFull: Rohrer, Bärbel IsPartOfRelationships: – BibEntity: Dates: – D: 23 M: 05 Text: 5/23/2014 Type: published Y: 2014 Identifiers: – Type: issn-print Value: 00219258 Numbering: – Type: volume Value: 289 – Type: issue Value: 21 Titles: – TitleFull: Journal of Biological Chemistry Type: main |
| ResultId | 1 |
