NFAT2 mediates high glucose-induced apoptosis in glomerular podocytes / 南方医科大学学报
Journal of Southern Medical University
; (12): 1270-1276, 2018.
Article
in Zh
| WPRIM
| ID: wpr-691183
Responsible library:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To determine whether hyperglycemia activates NFAT2 in cultured podocytes to cause podocyte apoptosis and explore the role of NFAT2 in high glucose-induced podocyte apoptosis.</p><p><b>METHODS</b>Immortalized mouse podocytes were cultured in the presence of normal (5.3 mmol/L) or high glucose (10, 20, 30, and 40 mmol/L) or pretreated with 11R-vivit (100 nmol/L) or cyclosporine A (500 nmol/L) before exposure to 20 mmol/L glucose for different durations (0.5-48 h). The activation of NFAT2 in the podocytes was detected using Western blotting and immunofluorescence assay. The role of NFAT2 in hyperglycemia-induced podocyte apoptosis was explored by observing the inhibition of NFAT2 activation by 11R-vivit using flow cytometry. Intracellular Ca was monitored in high glucose-treated podocytes using Fluo-3/AM. The mRNA and protein expressions of the apoptosis gene Bax were detected using real time-qPCR and Western blotting.</p><p><b>RESULTS</b>Exposure to high glucose in the medium time- and dose-dependently activated NFAT2 in cultured podocytes. Pretreatment with cyclosporine A or 11R- VIVIT completely blocked nuclear accumulation of NFAT2. Treatment with 11R- vivit also inhibited high glucoseinduced apoptosis in cultured podocytes. Exposure to high glucose obviously increased [Ca]I in the podocytes to cause activation of calcineurin and the subsequent increment of nuclear accumulation of NFAT2 and Bax expression.</p><p><b>CONCLUSIONS</b>High glucose-induced apoptosis in podocytes is mediated by calcineurin/NFAT2/Bax signaling pathway, which may serve as a potential target for therapeutic intervention.</p>
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WPRIM
Language:
Zh
Journal:
Journal of Southern Medical University
Year:
2018
Type:
Article