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- W1965658445 abstract "Purpose To evaluate the roles for PARP and Na+/H+-exchanger-1 (NHE-1) in early diabetes-induced changes in the retina and retinal capillary cellsMethods Control (C) and STZ-diabetic (D) rats were treated with/without the PARP inhibitors, 1,5-isoquinolinediol (ISO, 3 mgkg-1d-1 i.p.) or 10-(4-Methyl-piperazin-1-ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de]-anthracen-3-one (GPI 15427, 30 mgkg-1d-1), for 10 wks after 2 wks without treatment. Apoptosis was evaluated in flat-mounted retinas by TUNEL assay, and nitrotyrosine (NT), poly(ADP-ribose) (PAR), GFAP, BiP/GRP78 and GRP94 expressions by immunohistochemistry and Western blot analyses. Primary bovine retinal pericytes and endothelial cells were cultured with/without 0.6 mM palmitate, or in 5 mM or 30 mM glucose. Apoptosis was assessed by TUNEL and caspase-3 assays, superoxide production by ethidium fluorescence, and NT and PAR by immunocytochemistry.Results In the PARP study, the number of TUNEL-positive nuclei was increased ~4-fold in D, and this increase was prevented in D+ISO and D+GPI 15427. PARP inhibitors counteracted oxidative-nitrosative and endoplasmic reticulum stresses, and glial activation. Palmitate dose dependently increased superoxide production in cultured retinal cells. GPI 15427, 20 microM, prevented FFA-induced increase in the rate of apoptosis, and alleviated NT and PAR accumulation in both pericytes and endothelial cells. In the NHE-1 study, the specific NHE-1 inhibitor cariporide (10 microM) prevented high glucose-induced apoptosis, and alleviated oxidative-nitrosative stress and PAR accumulation in bovine retinal pericytes. In vivo studies in the STZ-diabetic rat model are in progress.Conclusion PARP and NHE-1 play an important role in early diabetes-induced changes in retina and retinal capillary cells." @default.
- W1965658445 created "2016-06-24" @default.
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- W1965658445 date "2008-09-04" @default.
- W1965658445 modified "2023-09-26" @default.
- W1965658445 title "PARP, Na+/H+-exchanger-1, and early diabetes-induced retinal changes" @default.
- W1965658445 doi "https://doi.org/10.1111/j.1755-3768.2008.6115.x" @default.
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