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Extracellular release of ATP mediated by cyclic mechanical stress leads to mobilization of AA in trabecular meshwork cells.

Publication ,  Journal Article
Luna, C; Li, G; Qiu, J; Challa, P; Epstein, DL; Gonzalez, P
Published in: Invest Ophthalmol Vis Sci
December 2009

PURPOSE: To investigate the mechanisms that mediate the release of ATP induced by cyclic mechanical stress (CMS) and the role of extracellular ATP in the mobilization of arachidonic acid (AA) and prostaglandin secretion. METHODS: Porcine trabecular meshwork (pTM) cells were subjected to CMS. Extracellular ATP was detected with a luciferin-luciferase assay in the presence or absence of transport inhibitors and a lipid raft disrupter. ATP vesicles were visualized with quinacrine. The release of AA (AA 1-14C) was measured with and without ATP, ATP inhibitors, and phospholipase-A and -C inhibitors. Prostaglandin E2 (PGE2) and viability were measured with ELISA and a lactate dehydrogenase assay, respectively. RESULTS: CMS induced ATP release that was inhibited by the vesicle inhibitors N-ethylmaleimide (NEM) and monensin. Lipid raft disruption significantly increased the extracellular ATP induced by CMS. CMS induced AA release (1-4-fold increase) and its metabolic product PGE2 (3.9-fold increase). The AA mobilization induced by CMS could be mimicked by the addition of extracellular ATP and was partially inhibited by a P2 antagonist, by an ATP inhibitor, and by inhibitors of phospholipase-A2 and -C. Addition of PGE2 (10 microM) to the media exerted cytoprotective effects against long-term CMS. CONCLUSIONS: Extracellular release of ATP induced by CMS in TM cells is mediated by exocytosis of ATP-enriched vesicles into lipid rafts. The resulting activation of purinergic receptors leads to mobilization of AA from the plasma membrane. The subsequent release of PGE could exert protective effects by preventing TM cell loss that may result from chronic exposure to CMS.

Duke Scholars

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

December 2009

Volume

50

Issue

12

Start / End Page

5805 / 5810

Location

United States

Related Subject Headings

  • Type C Phospholipases
  • Trabecular Meshwork
  • Swine
  • Stress, Mechanical
  • Phospholipases A2
  • Phospholipase A2 Inhibitors
  • Ophthalmology & Optometry
  • Monensin
  • Membrane Microdomains
  • Exocytosis
 

Citation

APA
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ICMJE
MLA
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Luna, C., Li, G., Qiu, J., Challa, P., Epstein, D. L., & Gonzalez, P. (2009). Extracellular release of ATP mediated by cyclic mechanical stress leads to mobilization of AA in trabecular meshwork cells. Invest Ophthalmol Vis Sci, 50(12), 5805–5810. https://doi.org/10.1167/iovs.09-3796
Luna, Coralia, Guorong Li, Jianming Qiu, Pratap Challa, David L. Epstein, and Pedro Gonzalez. “Extracellular release of ATP mediated by cyclic mechanical stress leads to mobilization of AA in trabecular meshwork cells.Invest Ophthalmol Vis Sci 50, no. 12 (December 2009): 5805–10. https://doi.org/10.1167/iovs.09-3796.
Luna C, Li G, Qiu J, Challa P, Epstein DL, Gonzalez P. Extracellular release of ATP mediated by cyclic mechanical stress leads to mobilization of AA in trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2009 Dec;50(12):5805–10.
Luna, Coralia, et al. “Extracellular release of ATP mediated by cyclic mechanical stress leads to mobilization of AA in trabecular meshwork cells.Invest Ophthalmol Vis Sci, vol. 50, no. 12, Dec. 2009, pp. 5805–10. Pubmed, doi:10.1167/iovs.09-3796.
Luna C, Li G, Qiu J, Challa P, Epstein DL, Gonzalez P. Extracellular release of ATP mediated by cyclic mechanical stress leads to mobilization of AA in trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2009 Dec;50(12):5805–5810.

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

December 2009

Volume

50

Issue

12

Start / End Page

5805 / 5810

Location

United States

Related Subject Headings

  • Type C Phospholipases
  • Trabecular Meshwork
  • Swine
  • Stress, Mechanical
  • Phospholipases A2
  • Phospholipase A2 Inhibitors
  • Ophthalmology & Optometry
  • Monensin
  • Membrane Microdomains
  • Exocytosis