PMID- 34020271
OWN - NLM
STAT- MEDLINE
DCOM- 20210622
LR  - 20210622
IS  - 1090-2414 (Electronic)
IS  - 0147-6513 (Linking)
VI  - 219
DP  - 2021 Aug
TI  - Role of Clusterin/NF-kappaB in the secretion of senescence-associated secretory 
      phenotype in Cr(VI)-induced premature senescent L-02 hepatocytes.
PG  - 112343
LID - S0147-6513(21)00454-1 [pii]
LID - 10.1016/j.ecoenv.2021.112343 [doi]
AB  - Hexavalent chromium [Cr(VI)] and its compounds have caused serious environmental 
      pollution and health damage. Senescent cells can actively change the surrounding 
      environment by secreting some factors, which are called senescence associated 
      secretory phenotype (SASP). Our previous work has confirmed that premature 
      senescent hepatocytes induced by Cr(VI) expressed high level of Clusterin (CLU) 
      and secrete interleukin-6 (IL-6) and IL-8. CLU is involved in the regulation of 
      tumor development and drug resistance, but whether CLU regulates SASP components 
      and participates in Cr(VI)-induced malignant transformation is unclear. In this 
      study we demonstrated that Cr(VI) induced the secretion of tumor promoting 
      components of SASP such as IL-6, IL-8, and granulocyte-macrophage colony 
      stimulating factor (GM-CSF) in senescent L-02 hepatocytes, while the levels of 
      the anti-tumor components of SASP such as chemokine (c-x-c motif) ligand-1 
      (CXCL-1) and monocyte chemoattractant protein-1 (MCP-1) were not altered. CLU 
      shRNA interference significantly reduced the levels of IL-6, IL-8, and GM-CSF in 
      the culture medium of senescent cells, suggesting CLU may regulate SASP. The 
      NF-kappaB inhibitor PDTC significantly alleviated Cr(VI)-induced increase of IL-6, 
      IL-8, and GM-CSF, confirming that NF-kappaB can regulate the tumor promoting 
      components of SASP. CLU shRNA interference aggravated the inhibitory effect of 
      PDTC on SASP secretion, indicating that CLU regulated the secretion of SASP in 
      Cr(VI)-induced senescent hepatocytes through the NF-kappaB signaling. We speculated 
      that SASP secreted by Cr(VI)-induced premature senescent hepatocytes was tightly 
      related to the carcinogenic effect of Cr(VI). Therefore, elucidation of upstream 
      regulatory mechanism of SASP is of great significance. In addition to further 
      clarifying the carcinogenic mechanisms associated with Cr(VI), we could also seek 
      out new targets for treatment of Cr(VI)-related cancer.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Liang, Yuehui
AU  - Liang Y
AD  - Xiangya School of Public Health, Central South University, Changsha 410078, PR 
      China.
FAU - Liang, Ningjuan
AU  - Liang N
AD  - Xiangya School of Public Health, Central South University, Changsha 410078, PR 
      China.
FAU - Ma, Yu
AU  - Ma Y
AD  - Xiangya School of Public Health, Central South University, Changsha 410078, PR 
      China.
FAU - Tang, Sixuan
AU  - Tang S
AD  - Xiangya School of Public Health, Central South University, Changsha 410078, PR 
      China.
FAU - Ye, Shuzi
AU  - Ye S
AD  - Xiangya School of Public Health, Central South University, Changsha 410078, PR 
      China.
FAU - Xiao, Fang
AU  - Xiao F
AD  - Xiangya School of Public Health, Central South University, Changsha 410078, PR 
      China. Electronic address: fangxiao@csu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20210518
PL  - Netherlands
TA  - Ecotoxicol Environ Saf
JT  - Ecotoxicology and environmental safety
JID - 7805381
RN  - 0 (Clusterin)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (RELA protein, human)
RN  - 0 (Transcription Factor RelA)
RN  - 0R0008Q3JB (Chromium)
RN  - 18540-29-9 (chromium hexavalent ion)
SB  - IM
MH  - Cellular Senescence/drug effects
MH  - Chromium/*toxicity
MH  - Clusterin/*metabolism
MH  - Hepatocytes/drug effects
MH  - Humans
MH  - Interleukin-6
MH  - NF-kappa B/*metabolism
MH  - Phenotype
MH  - Signal Transduction/drug effects
MH  - Transcription Factor RelA
OTO - NOTNLM
OT  - Clusterin
OT  - Hexavalent chromium [Cr(VI)]
OT  - Nuclear factor-kappa B (NF-kappaB)
OT  - Premature senescence
OT  - Senescence-associated secretory phenotype (SASP)
EDAT- 2021/05/22 06:00
MHDA- 2021/06/23 06:00
CRDT- 2021/05/21 20:25
PHST- 2020/12/31 00:00 [received]
PHST- 2021/05/10 00:00 [revised]
PHST- 2021/05/12 00:00 [accepted]
PHST- 2021/05/22 06:00 [pubmed]
PHST- 2021/06/23 06:00 [medline]
PHST- 2021/05/21 20:25 [entrez]
AID - S0147-6513(21)00454-1 [pii]
AID - 10.1016/j.ecoenv.2021.112343 [doi]
PST - ppublish
SO  - Ecotoxicol Environ Saf. 2021 Aug;219:112343. doi: 10.1016/j.ecoenv.2021.112343. 
      Epub 2021 May 18.