SIRT6 as a key event linking P53 and NRF2 counteracts APAP-induced hepatotoxicity through inhibiting oxidative stress and promoting hepatocyte proliferation.
10.1016/j.apsb.2020.06.016
- Author:
Yanying ZHOU
1
;
Xiaomei FAN
2
;
Tingying JIAO
1
;
Wenzhou LI
2
;
Panpan CHEN
1
;
Yiming JIANG
1
;
Jiahong SUN
1
;
Yixin CHEN
1
;
Pan CHEN
3
;
Lihuan GUAN
1
;
Yajie WEN
1
;
Min HUANG
1
;
Huichang BI
1
Author Information
1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
2. Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen 518102, China.
3. Department of Pharmacy, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
- Publication Type:Journal Article
- Keywords:
AAV, adeno-associated virus;
ALF, acute liver failure;
ALT, serum alanine aminotransferase;
APAP, acetaminophen;
ARE, antioxidant response element;
AST, aspartate aminotransferase;
Acetaminophen;
BCA, bicinchoninic acid;
BrdU, bromodeoxyuridine;
CCK-8, cell counting kit-8;
CCNA1, cyclin A1;
CCND1, cyclin D1;
CDK4, cyclin-dependent kinase 4;
CYP450, cytochromes P450;
Co-IP, co-immunoprecipitation;
DCF, dichlorofluorescein;
Dox, doxorubicin;
ECL, electrochemiluminescence;
GSH, glutathione;
GSTα, glutathianone S-transferase α;
GSTμ, glutathione S-transferase μ;
H&E, hematoxylin and eosin;
H3K56ac, histone H3 Nε-acetyl-lysines 56;
H3K9ac, histone H3 Nε-acetyl-lysines 9;
HO-1, heme oxygenase-1;
Hepatotoxicity;
KEAP1, Kelch-like ECH-associated protein 1;
LDH, lactate dehydrogenase;
NAPQI, N-acetyl p-benzoquinone imine;
NQO1, NAD(P)H quinone dehydrogenase 1;
NRF2;
NRF2, nuclear factor erythroid 2-related factor 2;
P53;
ROS, reactive oxygen species;
SIRT6;
SIRT6, sirtuin 6;
siRNA, small interfering RNA
- From:
Acta Pharmaceutica Sinica B
2021;11(1):89-99
- CountryChina
- Language:English
-
Abstract:
Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively.
