tert-Butylhydroquinone-induced formation of high-molecular-weight p62: A novel mechanism in the activation of Nrf2-Keap1

Chen，Yunfang1,2; Cao，Hua1,2; He，Wan1,2; Zhang，Xi1,2; Xu，Ruilian1,2

2022-07-01

10.1002/cbin.11849

CELL BIOLOGY INTERNATIONAL   Impact Factor & Quartile

1065-6995

1095-8355

The respiratory system is always exposed to air and is most vulnerable to attack by environmental free radicals. The nuclear factor E2-related factor 2-Kelch-like ECH-associated protein 1-antioxidant response element (Nrf2-Keap1-ARE) pathway and p62 are both involved in the oxidative stress response. However, the interplay between these two systems remains largely unknown. This study shows that treatment of L2 cells with tert-Butylhydroquinone (tBHQ) generates a high-molecular-weight (HMW) form of p62, leading to activation of the Nrf2-Keap1-ARE pathway. The levels of HMW-p62 increased as the tBHQ concentration increased, with concomitant decreases seen in the classical form of p62. Moreover, small interfering RNA targeting p62 increases Keap1 protein levels and inactivates the Nrf2-Keap1-ARE pathway. These results demonstrate that the Nrf2-Keap1 pathway is partially regulated by p62. tBHQ-induced HMW-p62 production may be a novel mechanism in the activation of the Nrf2-Keap1-ARE pathway.

high molecular weight Nrf2 oxidative stress p62 tert-Butylhydroquinone

SCI

English

Corresponding

Basic Research (Free Exploration) Project of Shenzhen Science and Technology Plan[JCYJ20190806151610947] ; Sanming project cultivation funds of Shenzhen People's Hospital[SYJY201903]

Cell Biology

Cell Biology

WOS:000824568700001

WILEY

MOLECULAR BIOLOGY & GENETICS

2-s2.0-85133895551

Web of Science

1.Department of Oncology,Shenzhen People's Hospital,The Second Clinical Medical College,Jinan University,Guangdong,China
2.Department of Oncology,The First Affiliated Hospital,Southern University of Science and Technology,Shenzen,China

Chen，Yunfang,Cao，Hua,He，Wan,et al. tert-Butylhydroquinone-induced formation of high-molecular-weight p62: A novel mechanism in the activation of Nrf2-Keap1[J]. CELL BIOLOGY INTERNATIONAL,2022.

Chen，Yunfang,Cao，Hua,He，Wan,Zhang，Xi,&Xu，Ruilian.(2022).tert-Butylhydroquinone-induced formation of high-molecular-weight p62: A novel mechanism in the activation of Nrf2-Keap1.CELL BIOLOGY INTERNATIONAL.

Chen，Yunfang,et al."tert-Butylhydroquinone-induced formation of high-molecular-weight p62: A novel mechanism in the activation of Nrf2-Keap1".CELL BIOLOGY INTERNATIONAL (2022).