PMID- 34968169
OWN - NLM
STAT- MEDLINE
DCOM- 20220223
LR  - 20220223
IS  - 2165-5987 (Electronic)
IS  - 2165-5979 (Print)
IS  - 2165-5979 (Linking)
VI  - 13
IP  - 1
DP  - 2022 Jan
TI  - The protective effects of etomidate against interleukin-1beta (IL-1beta)-induced 
      oxidative stress, extracellular matrix alteration and cellular senescence in 
      chondrocytes.
PG  - 985-994
LID - 10.1080/21655979.2021.2016085 [doi]
AB  - Osteoarthritis (OA) is a common chronic inflammatory disease associated with 
      aging. Etomidate is an intravenous anesthetic with profound antioxidant and 
      anti-inflammatory effects. We speculated that etomidate might exert a beneficial 
      effect on OA. Herein, we explored the effects of etomidate on interleukin-1beta 
      (IL-1beta)- induced chondrocytes. Our results prove that etomidate ameliorated the 
      IL-1beta-induced oxidative stress in C28/12 chondrocytes by decreasing and 
      increasing the reactive oxygen species (ROS) and glutathione peroxidase (GPx) 
      levels, respectively. Etomidate prevented the IL-1beta-induced increase in the 
      expressions of matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-13 
      (MMP-13) in C28/I2 chondrocytes at both mRNA and protein levels. It also caused a 
      significant reduction in the percentage of senescence-associated-beta-galactosidase 
      (SA-beta-Gal)-stained chondrocytes, while inducing elevated telomerase activity in 
      IL-1beta-treated C28/I2 chondrocytes. The expression levels of senescence 
      regulators, plasminogen activator inhibitor-1 (PAI-1) and p16, were also 
      inhibited by etomidate in IL-1beta-treated C28/I2 chondrocytes. In addition, 
      etomidate caused the activation of Adenosine 5'-monophosphate (AMP)-activated 
      protein kinase (AMPK), along with upregulated expression levels of phosphorylated 
      AMPKalpha and phosphorylated acetyl-Co A carboxylase (ACC). Moreover, blockage of 
      AMPK using compound C abolished the protective effects of etomidate on 
      IL-1beta-challenged C28/I2 chondrocytes. Taken together, these results demonstrate 
      that etomidate protected C28/I2 chondrocytes from IL-1beta-induced oxidative stress, 
      ECM degradation, and cellular senescence via activating AMPK signaling.
FAU - Yin, Miaomiao
AU  - Yin M
AD  - Department of Anesthesiology, The First People's Hospital of LianYungang, 
      Lianyungang City, Jiangsu Province, China.
FAU - Xu, Yinmei
AU  - Xu Y
AD  - Department of Anesthesiology, The First People's Hospital of LianYungang, 
      Lianyungang City, Jiangsu Province, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Bioengineered
JT  - Bioengineered
JID - 101581063
RN  - 0 (Interleukin-1beta)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - EC 2.7.4.3 (Adenylate Kinase)
RN  - EC 3.4.24.- (MMP13 protein, human)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - Z22628B598 (Etomidate)
SB  - IM
MH  - Adenylate Kinase/metabolism
MH  - Cell Line
MH  - Cellular Senescence/drug effects
MH  - Chondrocytes/*cytology/drug effects/metabolism
MH  - Etomidate/chemistry/*pharmacology
MH  - Extracellular Matrix/metabolism
MH  - Glutathione Peroxidase/metabolism
MH  - Humans
MH  - Interleukin-1beta/*adverse effects
MH  - Matrix Metalloproteinase 13/genetics/metabolism
MH  - Matrix Metalloproteinase 3/genetics/metabolism
MH  - Models, Biological
MH  - Molecular Structure
MH  - Osteoarthritis/chemically induced/drug therapy/genetics/*metabolism
MH  - Oxidative Stress/drug effects
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
PMC - PMC8805981
OTO - NOTNLM
OT  - AMP-activated protein kinase (AMPK)
OT  - Osteoarthritis (OA)
OT  - aging
OT  - chondrocytes
OT  - etomidate
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2021/12/31 06:00
MHDA- 2022/02/24 06:00
PMCR- 2021/12/30
CRDT- 2021/12/30 17:12
PHST- 2021/12/30 17:12 [entrez]
PHST- 2021/12/31 06:00 [pubmed]
PHST- 2022/02/24 06:00 [medline]
PHST- 2021/12/30 00:00 [pmc-release]
AID - 2016085 [pii]
AID - 10.1080/21655979.2021.2016085 [doi]
PST - ppublish
SO  - Bioengineered. 2022 Jan;13(1):985-994. doi: 10.1080/21655979.2021.2016085.