Acetylation Stimulates the Epithelial Sodium Channel by Reducing Its Ubiquitination and Degradation

Trichostatin A blocks aldosterone‐induced Na+ transport and control of serum‐ and glucocorticoid‐inducible kinase 1 in cortical collecting duct cells

“…The inhibition of mineralocorticoid receptor signalling which we now report may therefore be due, at least in part, to altered translocation of the mineralocorticoid receptor between the cytoplasm and the nucleus (Jimenez‐Canino et al, ). However, KDAC inhibition has also been shown to promote acetylation of ENaC itself (Butler, Staruschenko, & Snyder, ). This modification seems to block the ENaC internalisation process that appears to limit Na + transport in unstimulated cells (Blazer‐Yost & Nofziger, ; Gonzalez‐Rodriguez et al, ; Wang et al, ).…”

“…This modification seems to block the ENaC internalisation process that appears to limit Na + transport in unstimulated cells (Blazer‐Yost & Nofziger, ; Gonzalez‐Rodriguez et al, ; Wang et al, ). Rather than suppressing Na + absorption, these data therefore suggest that ENaC acetylation will augment Na + retention by increasing the surface abundance of the channel (Butler et al, ). While we cannot exclude the possibility that this process may augment Na + retention under certain conditions (Butler et al, ), our data show that TSA had no effect on basal Na + transport and did not modify the response to insulin.…”

“…Rather than suppressing Na + absorption, these data therefore suggest that ENaC acetylation will augment Na + retention by increasing the surface abundance of the channel (Butler et al, ). While we cannot exclude the possibility that this process may augment Na + retention under certain conditions (Butler et al, ), our data show that TSA had no effect on basal Na + transport and did not modify the response to insulin. It thus appears that inhibition of KDAC did not directly modify ENaC function under the conditions of our model.…”

“…The KDAC enzyme family contain at least eight members (KDAC1–8), and it is now clear that different KDACs can fulfil different physiological roles. The acetylation status of the mineralocorticoid receptor, for example, seems to be maintained by https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2617 (Lee et al, ), while https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2618 and KDAC5 are respectively thought to determine the acetylation status of hsp90 (Jimenez‐Canino et al, ) and ENaC (Butler et al, ). TSA is a broad spectrum KDAC inhibitor and thus has the potential to interfere with all of these events.…”

Post-Translational Modification and Natural Mutation of TRPC Channels

“…Acetylation of voltage-gated K + channel Kv2.1 led to internalization of the channel and attenuated apoptosis in INS-1 β-cells [93]. According to the report by Butler et al, acetylation of epithelial Na + channel elevated the channel abundance and plasma membrane expression by antagonizing ubiquitination and protein degradation [94]. Blockage of acetylation on K74 in voltage-dependent-anion channel was reported to decrease sperm motility [95].…”