PMID- 31175486
OWN - NLM
STAT- MEDLINE
DCOM- 20200702
LR  - 20200702
IS  - 1573-675X (Electronic)
IS  - 1360-8185 (Linking)
VI  - 24
IP  - 9-10
DP  - 2019 Oct
TI  - ATP induces caspase-3/gasdermin E-mediated pyroptosis in NLRP3 pathway-blocked 
      murine macrophages.
PG  - 703-717
LID - 10.1007/s10495-019-01551-x [doi]
AB  - ATP acts as a canonical activator to induce NLRP3 (NOD-like receptor family, 
      pyrin domain containing 3) inflammasome activation in macrophages, leading to 
      caspase-1/gasdermin D (GSDMD)-mediated pyroptosis. It remains unclear whether ATP 
      can induce pyroptosis in macrophages when the NLRP3 pathway is blocked by 
      pathogenic infection. In this study, we used cellular models to mimic such 
      blockade of NLRP3 activation: bone marrow-derived macrophages (BMDMs) treated 
      with NLRP3-specific inhibitor MCC950 and RAW264.7 cells deficient in ASC 
      (apoptosis-associated speck-like protein containing a caspase recruitment domain) 
      expression. The results showed that ATP treatment induced lytic cell death 
      morphologically resembling canonical pyroptosis in both MCC950-treated BMDMs and 
      RAW264.7 cells, but did not cause the activation of caspase-1 (by detecting 
      caspase-1p10 and mature interleukin-1beta) and cleavage of GSDMD. Instead, both 
      apoptotic initiator (caspase-8 and -9) and executioner (caspase-3 and -7) 
      caspases were evidently activated and gasdermin E (GSDME) was cleaved to generate 
      its N-terminal fragment (GSDME-NT) which executes pyroptosis. The GSDME-NT 
      production and lytic cell death induced by ATP were diminished by caspase-3 
      inhibitor. In BMDMs without MCC950 treatment, ATP induced the formation of ASC 
      specks which were co-localized with caspase-8; with MCC950 treatment, however, 
      ATP did not induced the formation of ASC specks. In RAW264.7 cells, knockdown of 
      GSDME by small interfering RNA attenuated ATP-induced lytic cell death and HMGB1 
      release into culture supernatants. Collectively, our results indicate that ATP 
      induces pyroptosis in macrophages through the caspase-3/GSDME axis when the 
      canonical NLRP3 pathway is blocked, suggestive of an alternative mechanism for 
      combating against pathogen evasion.
FAU - Zeng, Chen-Ying
AU  - Zeng CY
AD  - Department of Immunobiology, College of Life Science and Technology, Jinan 
      University, Guangzhou, China.
FAU - Li, Chen-Guang
AU  - Li CG
AD  - Department of Immunobiology, College of Life Science and Technology, Jinan 
      University, Guangzhou, China.
FAU - Shu, Jun-Xiang
AU  - Shu JX
AD  - Department of Immunobiology, College of Life Science and Technology, Jinan 
      University, Guangzhou, China.
FAU - Xu, Li-Hui
AU  - Xu LH
AD  - Department of Cell Biology, College of Life Science and Technology, Jinan 
      University, Guangzhou, China.
FAU - Ouyang, Dong-Yun
AU  - Ouyang DY
AD  - Department of Immunobiology, College of Life Science and Technology, Jinan 
      University, Guangzhou, China.
FAU - Mai, Feng-Yi
AU  - Mai FY
AD  - Department of Immunobiology, College of Life Science and Technology, Jinan 
      University, Guangzhou, China.
FAU - Zeng, Qiong-Zhen
AU  - Zeng QZ
AD  - Department of Immunobiology, College of Life Science and Technology, Jinan 
      University, Guangzhou, China.
FAU - Zhang, Cheng-Cheng
AU  - Zhang CC
AD  - Department of Immunobiology, College of Life Science and Technology, Jinan 
      University, Guangzhou, China.
FAU - Li, Rui-Man
AU  - Li RM
AD  - Department of Gynecology and Obstetrics, The First Affiliated Hospital of Jinan 
      University, Guangzhou, China. hqyylrm@126.com.
FAU - He, Xian-Hui
AU  - He XH
AUID- ORCID: 0000-0001-7433-7392
AD  - Department of Immunobiology, College of Life Science and Technology, Jinan 
      University, Guangzhou, China. thexh@jnu.edu.cn.
LA  - eng
GR  - 81773965/National Natural Science Foundation of China/International
GR  - 81673664/National Natural Science Foundation of China/International
GR  - 81873064/National Natural Science Foundation of China/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Apoptosis
JT  - Apoptosis : an international journal on programmed cell death
JID - 9712129
RN  - 0 (Gsdma protein, mouse)
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Adenosine Triphosphate/metabolism/*pharmacology
MH  - Animals
MH  - Caspase 1/metabolism
MH  - Caspase 3/*metabolism
MH  - Caspase 8/metabolism
MH  - Caspases/metabolism
MH  - Inflammasomes/metabolism
MH  - Macrophages/metabolism
MH  - Mice
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/genetics/*metabolism
MH  - Neoplasm Proteins/*metabolism
MH  - Pyroptosis/*drug effects
MH  - RAW 264.7 Cells
MH  - RNA Interference
OTO - NOTNLM
OT  - ATP
OT  - Caspase-3
OT  - Gasdermin E
OT  - Macrophages
OT  - Pyroptosis
EDAT- 2019/06/09 06:00
MHDA- 2020/07/03 06:00
CRDT- 2019/06/09 06:00
PHST- 2019/06/09 06:00 [pubmed]
PHST- 2020/07/03 06:00 [medline]
PHST- 2019/06/09 06:00 [entrez]
AID - 10.1007/s10495-019-01551-x [pii]
AID - 10.1007/s10495-019-01551-x [doi]
PST - ppublish
SO  - Apoptosis. 2019 Oct;24(9-10):703-717. doi: 10.1007/s10495-019-01551-x.