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Role of bestrophin‐3 protein in endoplasmic reticulum (ER)‐stress response and its regulation by reactive oxygen species (ROS) and ERK1/2 in kidney proximal tubule cells (PTC).
Author(s) -
Chakraborty Prabir K.,
Matchkov Vladimir V.,
Thévenod Frank
Publication year - 2010
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.24.1_supplement.770.1
Subject(s) - thapsigargin , endoplasmic reticulum , downregulation and upregulation , unfolded protein response , microbiology and biotechnology , reactive oxygen species , tunicamycin , chemistry , calcium signaling , signal transduction , biology , endocrinology , biochemistry , gene
The bestrophin (Best) protein family and its function as chloride channels have not been well characterized. Bestrophin‐3 is suggested to induce Ca 2+ activated currents in various tissues. We observed that rat Best‐3 was upregulated by Cd 2+ (25μM, 6h) both at the transcriptional and translational levels, in rat kidney PTC. Similar effects were observed with endoplasmic ER‐stress inducing agents, such as thapsigargin (3μM, 6h) and tunicamycin (6μM, 6h) but not with the calcium ionophore A21387 (1μM, 3 and 6h). The upregulation of Best‐3 by Cd 2+ was partly dependent on ROS because it could be prevented by the antioxidant α‐tocopherol (100μM). The regulation of Best‐3 expression was also dependent on ERK1/2, which is known to be activated by Cd 2+ , because the ERK1/2 inhibitor U0126 (10μM) prevented Cd 2+ ‐induced Best‐3 upregulation. Current studies aim to identify the transcription factor/s involved in Best‐3 gene expression. Our findings suggest that Best‐3 plays a role in ER stress response induced by Cd 2+ and other compounds and is regulated by ROS and ERK1/2 signaling. Funded by DFG TH 345/10‐1.