Cytoplasmic sirtuin 6 translocation mediated by p62 polyubiquitination plays a critical role in cadmium-induced kidney t
- PDF / 3,233,966 Bytes
- 15 Pages / 547.087 x 737.008 pts Page_size
- 51 Downloads / 170 Views
ORIGINAL ARTICLE
Cytoplasmic sirtuin 6 translocation mediated by p62 polyubiquitination plays a critical role in cadmium-induced kidney toxicity Keum-Young So & Byung-Hyun Park & Seon-Hee Oh
Received: 15 January 2020 / Accepted: 15 April 2020 # Springer Nature B.V. 2020
Abstract Sirtuin 6 (Sirt6) is important for maintaining kidney homeostasis and function. Cd exposure increases the risk of developing kidney diseases. However, the role of Sirt6 in kidney disease mechanisms is unclear. Here, we evaluated the role of Sirt6 in Cd-induced kidney toxicity. After Cd exposure, p62/sequestosome1 (SQSTM1), an autophagy substrate, accumulated in mouse kidney mesangial cells in monomeric and polyubiquitinated (polyUb) forms. Sirt6 accumulated in response to Cd treatment at concentrations below the half-maximal inhibitory concentration and decreased after 12 h of treatment. Sirt6 and p62 colocalized in the nucleus and redistributed to the cytosol after Cd treatment. Sirt6 was mainly present in nucleirich membrane fractions. Sirt6 interacted with p62. Ub, and microtubule-associated protein light chain 3 (LC3). Knockdown of p62 promoted Sirt6 nuclear Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10565-020-09528-2) contains supplementary material, which is available to authorized users. K.
Data Loading...
