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Hyperglycemia activates the Ca 2+ /calcineurin‐dependent transcription factor NFAT (Nuclear Factor of Activated T‐Cells) in retinal microvessels in vivo
Author(s) -
Zetterqvist Anna V.,
Öhman Jenny Nilsson,
Frutos Garcia Sergio,
McGuire Paul G.,
Bosc Laura Gonzalez,
Gomez Maria F.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1148.13
Subject(s) - nfat , calcineurin , endocrinology , medicine , microbiology and biotechnology , apyrase , biology , extracellular , chemistry , transplantation
Diabetic retinopathy is a major cause of blindness worldwide. The underlying pathogenesis is not clear but hyperglycemia has been identified as an important risk factor. Endothelial dysfunction, vasoconstriction and changes in Ca 2+ signaling have been shown to precede the onset of diabetic retinopathy. We have recently shown that high extracellular glucose activates NFAT in the smooth muscle cells of intact cerebral arteries. This effect involves the local release of extracellular nucleotides, such as UTP, acting on P2Y receptors, leading to increased [Ca 2+ ] i and subsequent activation of calcineurin. Activation of NFAT promotes cell proliferation and the expression of inflammatory markers, such as IL‐6, COX‐2 and osteopontin. We therefore hypothesize whether NFAT may act as a glucose‐sensor in the wall of retinal microvessels. Using confocal immunofluorescence microscopy we show that NFATc3 is expressed in the endothelium of murine retinal microvessels. Acute changes in blood glucose levels induced by IP‐GTT (glucose tolerance test) are readily detected by NFATc3 in vivo . NFAT activation is inhibited by a specific blocker of NFAT as well as by the ecto‐nucleotidase apyrase, suggesting the involvement of extracellular nucleotides also in the endothelial response to high glucose. Supported by: Swedish Heart & Lung Foundations, Swedish Research Medical Council & Royal Physiographic Society in Lund.