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The role of calcium-independent phospholipase A2γ in modulation of aqueous humor drainage and Ca2+ sensitization of trabecular meshwork contraction.
Pattabiraman, Padmanabhan P; Lih, Fred B; Tomer, Kenneth B; Rao, Ponugoti Vasantha.
Afiliación
  • Pattabiraman PP; Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA.
Am J Physiol Cell Physiol ; 302(7): C979-91, 2012 Apr 01.
Article en En | MEDLINE | ID: mdl-22237407
ABSTRACT
The contractile and relaxation characteristics of trabecular meshwork (TM) are presumed to influence aqueous humor (AH) drainage and intraocular pressure. The mechanisms underlying regulation of TM cell contractile properties, however, are not well understood. This study investigates the role of calcium-independent phospholipase A(2) (iPLA(2)), which controls eicosanoid synthesis, in regulation of TM cell contraction and AH outflow using mechanism-based isoform specific inhibitors (R)-bromoenol lactone (R-BEL, iPLA(2)γ specific) and (S)-bromoenol lactone (S-BEL, iPLA(2)ß specific). Immunohistochemical analysis revealed intense staining for both iPLA(2)ß and γ isoforms throughout the TM, juxtacanalicular tissue, and Schlemm's canal of human eye. Inhibition of iPLA(2)γ by R-BEL or small interfering RNA-mediated silencing of iPLA(2)γ expression induced dramatic changes in TM cell morphology, and decreased actin stress fibers, focal adhesions, and myosin light-chain (MLC) phosphorylation. AH outflow facility increased progressively and significantly in enucleated porcine eyes perfused with R-BEL. This response was associated with a significant decrease in TM tissue MLC phosphorylation and alterations in the morphology of aqueous plexi in R-BEL-perfused eyes. In contrast, S-BEL did not affect either of these parameters. Additionally, R-BEL-induced cellular relaxation of the TM was associated with a significant decrease in the levels of active Rho GTPase, phospho-MLC phosphatase, phospho-CPI-17, and arachidonic acid. Taken together, these observations demonstrate that iPLA(2)γ plays a significant and isoform-specific role in regulation of AH outflow facility by altering the contractile characteristics of the TM. The effects of iPLA(2)γ on TM contractile status appear to involve arachidonic acid and Rho GTPase signaling pathways.
Asunto(s)
Humor Acuoso/fisiología; Calcio/metabolismo; Fosfolipasas A2 Grupo IV/fisiología; Fosfolipasas A2 Grupo VI/genética; Fosfolipasas A2 Grupo VI/metabolismo; Malla Trabecular/fisiología; Actinas/genética; Actinas/metabolismo; Actomiosina/genética; Actomiosina/metabolismo; Animales; Humor Acuoso/efectos de los fármacos; Humor Acuoso/enzimología; Ácido Araquidónico/genética; Ácido Araquidónico/metabolismo; Células Cultivadas; Eicosanoides/genética; Eicosanoides/metabolismo; Adhesiones Focales/efectos de los fármacos; Adhesiones Focales/genética; Adhesiones Focales/metabolismo; Silenciador del Gen/efectos de los fármacos; Silenciador del Gen/fisiología; Fosfolipasas A2 Grupo IV/genética; Fosfolipasas A2 Grupo IV/metabolismo; Humanos; Inmunohistoquímica/métodos; Péptidos y Proteínas de Señalización Intracelular; Proteínas Musculares; Cadenas Ligeras de Miosina/genética; Cadenas Ligeras de Miosina/metabolismo; Naftalenos/farmacología; Fosfoproteínas Fosfatasas/genética; Fosfoproteínas Fosfatasas/metabolismo; Monoéster Fosfórico Hidrolasas/genética; Monoéster Fosfórico Hidrolasas/metabolismo; Fosforilación/efectos de los fármacos; Isoformas de Proteínas/genética; Isoformas de Proteínas/metabolismo; Pironas/farmacología; Transducción de Señal/efectos de los fármacos; Transducción de Señal/fisiología; Fibras de Estrés/efectos de los fármacos; Fibras de Estrés/genética; Fibras de Estrés/metabolismo; Porcinos; Malla Trabecular/efectos de los fármacos; Malla Trabecular/enzimología; Proteínas de Unión al GTP rho/genética; Proteínas de Unión al GTP rho/metabolismo

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Humor Acuoso / Malla Trabecular / Calcio / Fosfolipasas A2 Grupo VI / Fosfolipasas A2 Grupo IV Idioma: En Año: 2012 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Humor Acuoso / Malla Trabecular / Calcio / Fosfolipasas A2 Grupo VI / Fosfolipasas A2 Grupo IV Idioma: En Año: 2012 Tipo del documento: Article