Effect of overexpression of constitutively active PKCα on rat lacrimal gland protein secretion

被引:18
作者
Hodges, RR
Raddassi, I
Zoukhri, D
Toker, A
Kazlauskas, A
Dartt, DA
机构
[1] Schepens Eye Res Inst, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA
[3] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA
[4] Tufts Univ, Sch Dent Med, Boston, MA 02111 USA
关键词
D O I
10.1167/iovs.04-0508
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
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)-alpha plays a major role in cholinergic- and alpha(1)-adrenergic-induced protein secretion from the lacrimal gland. This study was undertaken to determine whether activation of PKCalpha alone would induce lacrimal gland protein secretion by examining the effects of overexpression of constitutively active PKCalpha. METHODS. Rat lacrimal gland acini were transduced with an adenovirus containing a gene for constitutively active PKCalpha. Protein secretion was measured in response to cholinergic and alpha(1)-adrenergic agonist stimulation. RESULTS. More than 84% of acinar cells were transduced, and PKCalpha expression was increased 176-fold. Western blot analysis using an antibody to phosphorylated (activated) PKCalpha indicated that the overexpressed PKCalpha was active, and basal secretion was increased. Cholinergic agonist-stimulated protein secretion was not stimulated above basal secretion, whereas alpha(1)-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 PKCalpha, possibly leading to the development of new treatments for dry eye syndromes.
引用
收藏
页码:3974 / 3981
页数:8
相关论文
共 42 条
[1]  
AKITA Y, 1994, J BIOL CHEM, V269, P4653
[2]   Constitutively active G alpha q and G alpha 13 trigger apoptosis through different pathways [J].
Althoefer, H ;
EversoleCire, P ;
Simon, MI .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (39) :24380-24386
[3]   ACTIVATION OF PROTEIN-KINASE-C DOES NOT CAUSE DESENSITIZATION IN RAT AND RABBIT MANDIBULAR ACINAR-CELLS [J].
BERRIE, CP ;
ELLIOTT, AC .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1994, 428 (02) :163-172
[4]   FUNCTIONAL INNERVATION OF LACRIMAL GLAND IN CAT - ORIGIN OF SECRETOMOTOR FIBERS IN LACRIMAL NERVE [J].
BOTELHO, SY ;
HISADA, M ;
FUENMAYO.N .
ARCHIVES OF OPHTHALMOLOGY, 1966, 76 (04) :581-&
[5]   Dominant negative Rab3D inhibits amylase release from mouse pancreatic acini [J].
Chen, XQ ;
Edwards, JAS ;
Logsdon, CD ;
Ernst, SA ;
Williams, JA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (20) :18002-18009
[6]  
DARTT DA, 1988, INVEST OPHTH VIS SCI, V29, P1726
[7]   Regulation of lacrimal gland secretion by neurotransmitters and the EGF family of growth factors [J].
Dartt, DA .
EXPERIMENTAL EYE RESEARCH, 2001, 73 (06) :741-752
[8]   LACRIMAL GLAND INOSITOL TRISPHOSPHATE ISOMER AND INOSITOL TETRAKISPHOSPHATE PRODUCTION [J].
DARTT, DA ;
DICKER, DM ;
RONCO, LV ;
KJELDSEN, IM ;
HODGES, RR ;
MURPHY, SA .
AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 259 (02) :G274-G281
[9]   Protein kinase C isozymes and the regulation of diverse cell responses [J].
Dempsey, EC ;
Newton, AC ;
Mochly-Rosen, D ;
Fields, AP ;
Reyland, ME ;
Insel, PA ;
Messing, RO .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2000, 279 (03) :L429-L438
[10]  
Ding CQ, 2001, INVEST OPHTH VIS SCI, V42, P2789