PMID- 34308846
OWN - NLM
STAT- MEDLINE
DCOM- 20210727
LR  - 20210914
IS  - 1673-4254 (Print)
IS  - 2663-0842 (Electronic)
IS  - 1673-4254 (Linking)
VI  - 41
IP  - 7
DP  - 2021 Jul 20
TI  - [Inhibition of mitochondrial reactive oxygen species reduces high glucose-induced 
      pyroptosis and ferroptosis in H9C2 cardiac myocytes].
PG  - 980-987
LID - 10.12122/j.issn.1673-4254.2021.07.03 [doi]
AB  - OBJECTIVE: To observe the effect of inhibiting mitochondrial oxidative stress and 
      NLRP3 inflammasomes on high glucose (HG)-induced pyroptosis and ferroptosis in 
      H9C2 cardiac muscle cells and explore the possible interactions between 
      mitochondrial reactive oxygen species (ROS) and inflammasomes. METHODS: H9C2 
      cells exposed to high glucose (35 mmol/L) were treated with the mitochondrial 
      antioxidant mitoquinone (MitoQ), the NLRP3 antagonist MCC950, or both MCC950 and 
      rotenone (a mitochondrial electron transport antagonist), and the cell viability 
      was measured with CCK-8 assay. The cellular and mitochondrial ROS levels were 
      measured using CellRox and Mitosox fluorescent probes, respectively. The cellular 
      NLRP3 inflammasome level was detected with immunofluorescence assay, and the 
      expressions of the key proteins related with pyroptosis and ferroptosis were 
      determined with Western blotting. RESULTS: HG exposure significantly lowered the 
      viability of H9C2 cells (P < 0.01), reduced the expression of GPX4 protein (a key 
      protein related with ferroptosis) (P < 0.01), and increased the fluorescence 
      intensities of NLRP3 (P < 0.01) and ROS (at both the cellular and mitochondrial 
      levels, P < 0.01) and the protein expressions of NLRP3 and GSDMD-NT (P < 0.01). 
      Treatment with either MitoQ or MCC950 significantly increased the viability of 
      HG-exposed cells (P < 0.01), increased GPX4 expression (P < 0.01), and reduced 
      the fluorescence intensities of NLRP3 (P < 0.01) and cellular and mitochondrial 
      ROS (P < 0.01) and the protein expressions of NLRP3 and GSDMD-NT (P < 0.05). 
      Compared with MCC950 treatment, treatment with both MCC950 and rotenone 
      significantly reduced the viability of HG-exposed cells (P < 0.01), lowered GPX4 
      expression (P < 0.01), and increased the fluorescence intensities of ROS and 
      NLRP3 (P < 0.01) and the protein levels of NLRP3 and GSDMD-NT (P < 0.05). 
      CONCLUSION: MitoQ inhibits mitochondrial ROS production to reduce HGinduced NLRP3 
      inflammasome activation and thus suppress pyroptosis and ferroptosis of cardiac 
      muscle cells. There may be an interaction between mitochondrial ROS and NLRP3 
      inflammasomes.
FAU - Wang, J
AU  - Wang J
AD  - Department of Physiology, Bengbu Medical College, Bengbu 233000, China.
AD  - Key Laboratory of Basic and Clinical Cardiovascular Diseases, Bengbu Medical 
      College, Bengbu 233000, China.
FAU - Liang, H
AU  - Liang H
AD  - Department of Physiology, Bengbu Medical College, Bengbu 233000, China.
AD  - Key Laboratory of Basic and Clinical Cardiovascular Diseases, Bengbu Medical 
      College, Bengbu 233000, China.
FAU - Fang, D
AU  - Fang D
AD  - Department of Physiology, Bengbu Medical College, Bengbu 233000, China.
AD  - Key Laboratory of Basic and Clinical Cardiovascular Diseases, Bengbu Medical 
      College, Bengbu 233000, China.
FAU - Huang, Y
AU  - Huang Y
AD  - Department of Physiology, Bengbu Medical College, Bengbu 233000, China.
AD  - Key Laboratory of Basic and Clinical Cardiovascular Diseases, Bengbu Medical 
      College, Bengbu 233000, China.
FAU - Miao, Y
AU  - Miao Y
AD  - Department of Physiology, Bengbu Medical College, Bengbu 233000, China.
AD  - Key Laboratory of Basic and Clinical Cardiovascular Diseases, Bengbu Medical 
      College, Bengbu 233000, China.
FAU - Yu, Y
AU  - Yu Y
AD  - Department of Physiology, Bengbu Medical College, Bengbu 233000, China.
AD  - Key Laboratory of Basic and Clinical Cardiovascular Diseases, Bengbu Medical 
      College, Bengbu 233000, China.
FAU - Gao, Q
AU  - Gao Q
AD  - Department of Physiology, Bengbu Medical College, Bengbu 233000, China.
AD  - Key Laboratory of Basic and Clinical Cardiovascular Diseases, Bengbu Medical 
      College, Bengbu 233000, China.
LA  - chi
PT  - Journal Article
PL  - China
TA  - Nan Fang Yi Ke Da Xue Xue Bao
JT  - Nan fang yi ke da xue xue bao = Journal of Southern Medical University
JID - 101266132
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Reactive Oxygen Species)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - *Ferroptosis
MH  - Glucose/toxicity
MH  - Inflammasomes
MH  - Myocytes, Cardiac
MH  - NLR Family, Pyrin Domain-Containing 3 Protein
MH  - *Pyroptosis
MH  - Reactive Oxygen Species
PMC - PMC8329685
OTO - NOTNLM
OT  - NLRP3 inflammasome
OT  - ferroptosis
OT  - high glucose
OT  - mitochondrial reactive oxygen species
OT  - pyroptosis
EDAT- 2021/07/27 06:00
MHDA- 2021/07/28 06:00
PMCR- 2021/07/20
CRDT- 2021/07/26 08:53
PHST- 2021/07/26 08:53 [entrez]
PHST- 2021/07/27 06:00 [pubmed]
PHST- 2021/07/28 06:00 [medline]
PHST- 2021/07/20 00:00 [pmc-release]
AID - nfykdxxb-41-7-980 [pii]
AID - 10.12122/j.issn.1673-4254.2021.07.03 [doi]
PST - ppublish
SO  - Nan Fang Yi Ke Da Xue Xue Bao. 2021 Jul 20;41(7):980-987. doi: 
      10.12122/j.issn.1673-4254.2021.07.03.