Premium
Nuclear transcription factor kappa B (NF‐kB) mediates ROS and PKC‐induced decrease in TRPC6 protein expression in human glomerular mesangial cells (HMCs)
Author(s) -
Ma Rong,
Wang Yanxia,
Ding Min
Publication year - 2012
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.26.1_supplement.687.2
Subject(s) - protein kinase c , trpc6 , gene knockdown , nf κb , chemistry , transcription factor , microbiology and biotechnology , nfkb1 , signal transduction , biology , receptor , apoptosis , biochemistry , gene , transient receptor potential channel
We recently demonstrated that high ambient glucose significantly decreased the expression of TRPC6 at protein level in cultured HMCs through a ROS/PKC pathway. The present study was carried out to examine if NF‐κB is a downstream molecule of ROS/PKC in the pathway of suppressing TRPC6 protein expression in HMCs. Serum‐starved HMCs were treated with 200 μM H 2 O 2 for 6 hours or with 1 μM PMA for 2 hours significantly reduced TRPC6 protein expression. These ROS and PKC effects were significantly prevented by pre‐treating the cells with NF‐κB activation inhibitor at 10 μM for 30 min. Both H 2 O 2 and PMA, but not PMA inactive analog 4α‐PDD phosphorylated the inhibitory κBα (IκBα) and stimulated the degradation of IκBα in a time dependent manner. Furthermore, activation of NF‐κB by knockdown of IκBα using siRNA significantly reduced abundance of TRPC6 protein in HMCs, a reminiscent of H 2 O 2 and PMA effect on TRPC6 protein expression. Importantly, either H 2 O 2 or PMA treatment dramatically increased nuclear expression of NF‐ κB p65/p50 subunits in a time dependent manner in HMCs, suggesting activation of NF‐κB in response to both ROS and PKC activation. These results suggest that NF‐κB is a mediator downstream ROS and PKC for suppression of TRPC6 expression in HMCs. (Supported by NIH)