PMID- 36521686
OWN - NLM
STAT- MEDLINE
DCOM- 20230102
LR  - 20230217
IS  - 1879-2596 (Electronic)
IS  - 0167-4889 (Linking)
VI  - 1870
IP  - 2
DP  - 2023 Feb
TI  - Sirt3 activates autophagy to prevent DOX-induced senescence by inactivating 
      PI3K/AKT/mTOR pathway in A549 cells.
PG  - 119411
LID - S0167-4889(22)00203-8 [pii]
LID - 10.1016/j.bbamcr.2022.119411 [doi]
AB  - Sirtuin 3 (Sirt3), a mitochondrial deacetylase, regulates mitochondrial redox 
      homeostasis and autophagy and is involved in physiological and pathological 
      processes such as aging, cellular metabolism, and tumorigenesis. We here 
      investigate how Sirt3 regulates doxorubicin (DOX)-induced senescence in lung 
      cancer A549 cells. Sirt3 greatly reduced DOX-induced upregulation of senescence 
      marker proteins p53, p16, p21 and SA-beta-Gal activity as well as ROS levels. 
      Notably, Sirt3 reversed DOX-induced autophagic flux blockage, as shown by 
      increased p62 degradation and LC3II/LC3I ratio. Importantly, the autophagy 
      inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) partially abolished the 
      antioxidant stress and antiaging effects of Sirt3, while the autophagy activator 
      rapamycin (Rap) potentiated these effects of Sirt3, demonstrating that autophagy 
      mediates the anti-aging effects of Sirt3. Additionally, Sirt3 inhibited the 
      DOX-induced activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian 
      target of rapamycin (mTOR) signaling pathway, which in turn activated autophagy. 
      The PI3K inhibitor LY294002 promoted the antioxidant stress and antiaging effects 
      of Sirt3, while the AKT activator SC-79 reversed these effects of Sirt3. Taken 
      together, Sirt3 counteracts DOX-induced senescence by improving autophagic flux.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Fan, Xuhong
AU  - Fan X
AD  - Department of Pain Management, the First Affiliated Hospital of Jinan University, 
      Guangzhou 510630, China.
FAU - He, Yuting
AU  - He Y
AD  - Department of Pain Management, the First Affiliated Hospital of Jinan University, 
      Guangzhou 510630, China.
FAU - Wu, Guihao
AU  - Wu G
AD  - Department of Pain Management, the First Affiliated Hospital of Jinan University, 
      Guangzhou 510630, China.
FAU - Chen, Hongce
AU  - Chen H
AD  - MOE Key Laboratory of Laser Life Science, Guangdong Provincial Key Laboratory of 
      Laser Life Science, College of Biophotonics, South China Normal University, 
      Guangzhou 510631, China.
FAU - Cheng, Xuecheng
AU  - Cheng X
AD  - MOE Key Laboratory of Laser Life Science, Guangdong Provincial Key Laboratory of 
      Laser Life Science, College of Biophotonics, South China Normal University, 
      Guangzhou 510631, China.
FAU - Zhan, Yongtong
AU  - Zhan Y
AD  - Department of Pain Management, the First Affiliated Hospital of Jinan University, 
      Guangzhou 510630, China.
FAU - An, Chunchun
AU  - An C
AD  - MOE Key Laboratory of Laser Life Science, Guangdong Provincial Key Laboratory of 
      Laser Life Science, College of Biophotonics, South China Normal University, 
      Guangzhou 510631, China.
FAU - Chen, Tongsheng
AU  - Chen T
AD  - MOE Key Laboratory of Laser Life Science, Guangdong Provincial Key Laboratory of 
      Laser Life Science, College of Biophotonics, South China Normal University, 
      Guangzhou 510631, China.
FAU - Wang, Xiaoping
AU  - Wang X
AD  - Department of Pain Management, the First Affiliated Hospital of Jinan University, 
      Guangzhou 510630, China. Electronic address: txp2938@jnu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221212
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Cell Res
JT  - Biochimica et biophysica acta. Molecular cell research
JID - 101731731
RN  - EC 3.5.1.- (Sirtuin 3)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - 0 (Antioxidants)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 80168379AG (Doxorubicin)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Humans
MH  - *Sirtuin 3/genetics/metabolism/pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Phosphatidylinositol 3-Kinase/pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - A549 Cells
MH  - Antioxidants/pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Doxorubicin/pharmacology
MH  - Sirolimus/pharmacology
MH  - Autophagy
OTO - NOTNLM
OT  - Autophagy
OT  - PI3K/AKT/mTOR pathway
OT  - Senescence
OT  - Sirtuin 3
COIS- Declaration of competing interest No conflict of interest.
EDAT- 2022/12/16 06:00
MHDA- 2023/01/03 06:00
CRDT- 2022/12/15 19:26
PHST- 2022/08/28 00:00 [received]
PHST- 2022/11/27 00:00 [revised]
PHST- 2022/12/03 00:00 [accepted]
PHST- 2022/12/16 06:00 [pubmed]
PHST- 2023/01/03 06:00 [medline]
PHST- 2022/12/15 19:26 [entrez]
AID - S0167-4889(22)00203-8 [pii]
AID - 10.1016/j.bbamcr.2022.119411 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Cell Res. 2023 Feb;1870(2):119411. doi: 
      10.1016/j.bbamcr.2022.119411. Epub 2022 Dec 12.