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Robin R. Hodges, Isabelle Raddassi, Driss Zoukhri, Alex Toker, Andrius Kazlauskas, Darlene A. Dartt; Effect of Overexpression of Constitutively Active PKCα on Rat Lacrimal Gland Protein Secretion. Invest. Ophthalmol. Vis. Sci. 2004;45(11):3974-3981. doi: 10.1167/iovs.04-0508.
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purpose. The lacrimal gland secretes water, electrolytes, and protein into the tear film. Decreased secretion from the lacrimal gland can lead to dry eye syndromes with deleterious effects on vision. Protein kinase C (PKC)-α plays a major role in cholinergic- and α1-adrenergic–induced protein secretion from the lacrimal gland. This study was undertaken to determine whether activation of PKCα alone would induce lacrimal gland protein secretion by examining the effects of overexpression of constitutively active PKCα.
methods. Rat lacrimal gland acini were transduced with an adenovirus containing a gene for constitutively active PKCα. Protein secretion was measured in response to cholinergic and α1-adrenergic agonist stimulation.
results. More than 84% of acinar cells were transduced, and PKCα expression was increased 176-fold. Western blot analysis using an antibody to phosphorylated (activated) PKCα indicated that the overexpressed PKCα was active, and basal secretion was increased. Cholinergic agonist–stimulated protein secretion was not stimulated above basal secretion, whereas α1-adrenergic-agonist–stimulated protein secretion was increased in transduced acini.
conclusions. Basal lacrimal gland protein secretion can be stimulated by bypassing the release of neurotransmitters and activating PKCα, possibly leading to the development of new treatments for dry eye syndromes.
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