h-89 and Cataract

h-89 has been researched along with Cataract* in 1 studies

Other Studies

1 other study(ies) available for h-89 and Cataract

Article	Year
Induction of cortical cataracts in cultured mouse lenses with H-89, an inhibitor of protein kinase A. Current eye research, 2003, Volume: 27, Issue:5 To compare the effects of two serine-threonine protein kinase inhibitors in a mouse lens culture system previously designed to investigate cortical cataracts caused by L-buthionine sulfoximine (BSO), inhibitor of GSH biosynthesis.. Cataract development in HL-1 medium was evaluated visually or by measurement of lens Na+/K+ ratio through atomic absorption. Protein changes were evaluated by 32P-labeling, 2D-gel electrophoresis, phosphorimaging and mass spectrometry. Results. H-7 (50 microM), inhibitor of protein kinase A (PKA) and protein kinase C (PKC), did not cause cataracts, but inhibited BSO cataract development. By contrast, 25 microM H-89, selective inhibitor of PKA, caused large annular cortical cataracts and 100-fold elevation of Na+/K+ within 30 hr in day 10 lenses, in either the presence or absence of BSO. H-89 cataracts were also seen in day 12 and day 21 lenses. 32P-labeling of day 12 lenses pretreated with H-89 displayed more than 80% decrease in phosphorylation of alphaA crystallin, a known substrate of PKA, in the insoluble protein fraction. 2D-gel electrophoresis of day 12 H-89 cataract lens fractions revealed limited degradation of alpha and beta crystallins, degradation of cytoskeletal proteins, and elevated lens Ca2+ (>4 nmol/mg wet wt.), suggesting Ca2+-activated proteolysis. Conclusions. High Na+/K+ cataracts are induced by H-89, selective inhibitor of PKA, but not by H-7, an inhibitor of both PKA and PKC that impeded BSO-induced Na+/K+ elevation and cataract. These results suggest contrasting effects of PKA and PKC on lens cation transport and cortical cataract development. Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; alpha-Crystallin A Chain; Animals; Animals, Newborn; Buthionine Sulfoximine; Calcium; Cataract; Cyclic AMP-Dependent Protein Kinases; Electrophoresis, Gel, Two-Dimensional; Enzyme Inhibitors; Female; Isoquinolines; Lens Cortex, Crystalline; Male; Mice; Organ Culture Techniques; Phosphorylation; Potassium; Pregnancy; Protein Kinase C; Sodium; Spectrophotometry, Atomic; Sulfonamides	2003

Article

Year

Induction of cortical cataracts in cultured mouse lenses with H-89, an inhibitor of protein kinase A.

Current eye research, 2003, Volume: 27, Issue:5

To compare the effects of two serine-threonine protein kinase inhibitors in a mouse lens culture system previously designed to investigate cortical cataracts caused by L-buthionine sulfoximine (BSO), inhibitor of GSH biosynthesis.. Cataract development in HL-1 medium was evaluated visually or by measurement of lens Na+/K+ ratio through atomic absorption. Protein changes were evaluated by 32P-labeling, 2D-gel electrophoresis, phosphorimaging and mass spectrometry. Results. H-7 (50 microM), inhibitor of protein kinase A (PKA) and protein kinase C (PKC), did not cause cataracts, but inhibited BSO cataract development. By contrast, 25 microM H-89, selective inhibitor of PKA, caused large annular cortical cataracts and 100-fold elevation of Na+/K+ within 30 hr in day 10 lenses, in either the presence or absence of BSO. H-89 cataracts were also seen in day 12 and day 21 lenses. 32P-labeling of day 12 lenses pretreated with H-89 displayed more than 80% decrease in phosphorylation of alphaA crystallin, a known substrate of PKA, in the insoluble protein fraction. 2D-gel electrophoresis of day 12 H-89 cataract lens fractions revealed limited degradation of alpha and beta crystallins, degradation of cytoskeletal proteins, and elevated lens Ca2+ (>4 nmol/mg wet wt.), suggesting Ca2+-activated proteolysis. Conclusions. High Na+/K+ cataracts are induced by H-89, selective inhibitor of PKA, but not by H-7, an inhibitor of both PKA and PKC that impeded BSO-induced Na+/K+ elevation and cataract. These results suggest contrasting effects of PKA and PKC on lens cation transport and cortical cataract development.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; alpha-Crystallin A Chain; Animals; Animals, Newborn; Buthionine Sulfoximine; Calcium; Cataract; Cyclic AMP-Dependent Protein Kinases; Electrophoresis, Gel, Two-Dimensional; Enzyme Inhibitors; Female; Isoquinolines; Lens Cortex, Crystalline; Male; Mice; Organ Culture Techniques; Phosphorylation; Potassium; Pregnancy; Protein Kinase C; Sodium; Spectrophotometry, Atomic; Sulfonamides

2003