Impairment of conjunctival glutathione secretion and ion transport by oxidative stress in an adenovirus type 5 ocular infection model of pigmented rabbits.

Impairment of conjunctival glutathione secretion and ion transport by oxidative stress in an adenovirus type 5 ocular infection model of pigmented rabbits. Research Abstract Details 

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Impairment of conjunctival glutathione secretion and ion transport by oxidative stress in an adenovirus type 5 ocular infection model of pigmented rabbits. Abstract Text:

Ram Kannan,Hovhannes J Gukasyan,Wenzheng Zhang,Melvin D Trousdale,Kwang-Jin Kim,Vincent H L Lee,

Conjunctival epithelial cells of pigmented rabbits secrete reduced glutathione (GSH) into the apical (mucosal) fluid. The aim of the current study was to determine the effect of oxidative stress resulting from viral infection and that of GSH supplementation on redox status, GSH, and ion transport in freshly excised conjunctival tissues and epithelial cell layers in primary culture (RCEC) of adenovirus type 5 (Ad5)-infected rabbits. Lipid peroxidation (LPO) products, nitric oxide (NO), and expression of nitric oxide synthase (NOS2) were quantitated as a function of time after viral inoculation. Unidirectional fluxes of [3H]GSH and changes in short-circuit current (Isc) from mucosal supplementation of Ad5-inoculated conjunctival tissues with GSH and glutathione monoethyl ester (GSH-MEE) were also measured. Ad5 inoculation significantly decreased conjunctival GSH level by 19, 45, 48, and 50% at 8, 24, 48, and 72 h postinfection, respectively. LPO product and NO levels increased significantly (2- and 100-fold, respectively) above that of uninfected controls on Day 3 post-Ad5 inoculation, and co-treatment with GSH-MEE and tocopherol succinate abolished this effect. NO levels showed a progressive increase post-Ad5 inoculation, reaching 0.22 +/- 0.06, 8.12 +/- 0.91, and 2.05 +/- 0.65 microM on Days 1, 3, and 5, respectively, and the highest level was observed on the day of maximal viral replication (Day 3). A very significant induction of the expression of NOS2 on Days 1, 3, and 5 post-Ad5 inoculation was observed. Uninfected control conjunctival tissues displayed a net serosal-to-mucosal GSH flux (Jsm), where the mucosal-to-serosal flux (Jms) was approximately 14 pmol h(-1) cm(-2) and the Jsm was approximately 22 pmol h(-1) cm(-2). In Ad5-inoculated rabbits similar GSH flux was observed in both the sm and ms directions, and the net GSH flux was negligible. Isc and potential difference (PD) across conjunctival tissues of Ad5-inoculated rabbits decreased by > or = 50% compared with control, while the transepithelial electrical resistance (TEER) remained unchanged. Mucosal, but not serosal, superfusion of GSH or GSH-MEE in Ad5-inoculated conjunctival tissues increased the Isc by up to 40% in approximately 100 min. Our results show that net secretion of GSH across rabbit conjunctiva is totally blocked after Ad5 inoculation and active ion transport rate decreased by approximately 50%. Decreased net GSH secretion into mucosal fluid after Ad5 infection may have resulted from a decreased intracellular GSH pool due to oxyradical-induced changes in redox status and lower active ion transport. Mucosal treatment of Ad5-infected conjunctival tissues with pharmacological levels of GSH appears to transstimulate mucosal GSH secretion and restore active ion transport activity, suggesting a potentially useful therapeutic regimen for ocular infections.

Impairment of conjunctival glutathione secretion and ion transport by oxidative stress in an adenovirus type 5 ocular infection model of pigmented rabbits. Publishing Authors By Initials

R Kannan,HJ Gukasyan,W Zhang,MD Trousdale,KJ Kim,VH Lee,

For similar heterocyclic compounds: heterocyclic compounds, 2-ring: benzopyrans: vitamin e research abstracts see: heterocyclic compounds: heterocyclic compounds, 2-ring: benzopyrans: vitamin e research

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Impairment of conjunctival glutathione secretion and ion transport by oxidative stress in an adenovirus type 5 ocular infection model of pigmented rabbits. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Free radical biology & medicine

VOLUME: 37

Page Numbers: 229-38

Journal Abbreviation: Free Radic. Biol. Med.

ISSN: 0891-5849

DAY: 15

MONTH: Jul

YEAR: 2004

Impairment of conjunctival glutathione secretion and ion transport by oxidative stress in an adenovirus type 5 ocular infection model of pigmented rabbits. Information

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LANGUAGE: eng

NlmUniqueID: 8709159

Impairment of conjunctival glutathione secretion and ion transport by oxidative stress in an adenovirus type 5 ocular infection model of pigmented rabbits. Keywords Mesh Terms:

KEYWORDS: Vitamin E

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Impairment of conjunctival glutathione secretion and ion transport by oxidative stress in an adenovirus type 5 ocular infection model of pigmented rabbits. Information

Substance Name: Nitric Oxide Synthase

Registry Number: EC 1.14.13.39

Grant and Affiliation Information for Impairment of conjunctival glutathione secretion and ion transport by oxidative stress in an adenovirus type 5 ocular infection model of pigmented rabbits.

AFFILIATION: Doheny Eye Institute, Schools of Pharmacy, Medicine, and Engineering, University of Southern California, Los Angeles 90089, USA. rkannan@dohenyeyeinstitute.org

Country: United States

AGENCY: United States NHLBI

GRANT: HL64365

ACRONYM: HL

MEDLINETA: Free Radic Biol Med

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