PMID- 27731349
OWN - NLM
STAT- MEDLINE
DCOM- 20180425
LR  - 20201019
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Oct 12
TI  - TRPM2 regulates TXNIP-mediated NLRP3 inflammasome activation via interaction with 
      p47 phox under high glucose in human monocytic cells.
PG  - 35016
LID - 10.1038/srep35016 [doi]
LID - 35016
AB  - Excessive production of reactive oxygen species (ROS) induced by hyperglycemia 
      increased the secretion of interleukin-1beta (IL-1beta), which contributes to the 
      pathogenesis of diabetes and its complications. Although high glucose 
      (HG)-induced oxidative stress and aberrant Ca(2+) channels activity causes an 
      increase in transmembrane Ca(2+) influx, however the relative contribution of 
      Transient receptor potential (TRP) channels is not well studied. Here, we 
      identified that HG (30 mM glucose for 48 h) induced the activation of the 
      NLRP3-ASC inflammasome, leading to caspase-1 activation, and IL-1beta and IL-18 
      secretion in human monocytic cell lines. Moreover, we used a hyperglycemia model 
      in U937 monocytes, showing that the activation of TRPM2 was augmented, and 
      TRPM2-mediated Ca(2+) influx was critical for NLRP3 inflammasome activation. This 
      pathway involved NADPH oxidase-dependent ROS production and TXNIP-NLRP3 
      inflammasome pathway. Furthermore, the inhibition of TRPM2 reduced ROS production 
      and lowered NADPH oxidase activity via cooperatively interaction with p47 phox in 
      response to HG. These results provided a mechanistic linking between 
      TRPM2-mediated Ca(2+) influx and p47 phox signaling to induce excess ROS 
      production and TXNIP-mediated NLRP3 inflammasome activation under HG, and 
      suggested that TRPM2 represented a potential target for alleviating NLRP3 
      inflammasome activation related to hyperglycemia-induced oxidative stress in Type 
      2 diabetes Mellitus (T2DM).
FAU - Tseng, Hisa Hui Ling
AU  - Tseng HH
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, 
      Macau, China.
FAU - Vong, Chi Teng
AU  - Vong CT
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, 
      Macau, China.
FAU - Kwan, Yiu Wa
AU  - Kwan YW
AD  - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of 
      Hong Kong, Shatin, N.T., Hong Kong, China.
FAU - Lee, Simon Ming-Yuen
AU  - Lee SM
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, 
      Macau, China.
FAU - Hoi, Maggie Pui Man
AU  - Hoi MP
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, 
      Macau, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161012
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Carrier Proteins)
RN  - 0 (IL18 protein, human)
RN  - 0 (IL1B protein, human)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (NLRP3 protein, human)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (TRPM Cation Channels)
RN  - 0 (TRPM2 protein, human)
RN  - 0 (TXNIP protein, human)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.1 (neutrophil cytosolic factor 1)
RN  - EC 3.4.22.36 (Caspase 1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Carrier Proteins/*metabolism
MH  - Caspase 1/metabolism
MH  - Cell Line
MH  - Gene Expression Regulation/drug effects
MH  - Glucose/*pharmacology
MH  - Humans
MH  - Hyperglycemia/metabolism
MH  - Inflammasomes/metabolism
MH  - Interleukin-18/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Models, Biological
MH  - Monocytes/cytology/*drug effects/metabolism
MH  - NADPH Oxidases/*metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - TRPM Cation Channels/*metabolism
PMC - PMC5059733
EDAT- 2016/10/13 06:00
MHDA- 2018/04/26 06:00
PMCR- 2016/10/12
CRDT- 2016/10/13 06:00
PHST- 2016/07/07 00:00 [received]
PHST- 2016/09/21 00:00 [accepted]
PHST- 2016/10/13 06:00 [entrez]
PHST- 2016/10/13 06:00 [pubmed]
PHST- 2018/04/26 06:00 [medline]
PHST- 2016/10/12 00:00 [pmc-release]
AID - srep35016 [pii]
AID - 10.1038/srep35016 [doi]
PST - epublish
SO  - Sci Rep. 2016 Oct 12;6:35016. doi: 10.1038/srep35016.