PMID- 34206390
OWN - NLM
STAT- MEDLINE
DCOM- 20210923
LR  - 20210923
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 11
IP  - 7
DP  - 2021 Jun 22
TI  - A Metalloproteinase Induces an Inflammatory Response in Preadipocytes with the 
      Activation of COX Signalling Pathways and Participation of Endogenous 
      Phospholipases A(2).
LID - 10.3390/biom11070921 [doi]
LID - 921
AB  - Matrix metalloproteinases (MMPs) are proteolytic enzymes that have been 
      associated with the pathogenesis of inflammatory diseases and obesity. Adipose 
      tissue in turn is an active endocrine organ capable of secreting a range of 
      proinflammatory mediators with autocrine and paracrine properties, which 
      contribute to the inflammation of adipose tissue and adjacent tissues. However, 
      the potential inflammatory effects of MMPs in adipose tissue cells are still 
      unknown. This study investigates the effects of BmooMPalpha-I, a single-domain snake 
      venom metalloproteinase (SVMP), in activating an inflammatory response by 3T3-L1 
      preadipocytes in culture, focusing on prostaglandins (PGs), cytokines, and 
      adipocytokines biosynthesis and mechanisms involved in prostaglandin E(2) 
      (PGE(2)) release. The results show that BmooMPalpha-I induced the release of PGE(2), 
      prostaglandin I(2) (PGI(2)), monocyte chemoattractant protein-1 (MCP-1), and 
      adiponectin by preadipocytes. BmooMPalpha-I-induced PGE(2) biosynthesis was dependent 
      on group-IIA-secreted phospholipase A(2) (sPLA(2)-IIA), cytosolic phospholipase 
      A(2)-alpha (cPLA(2)-alpha), and cyclooxygenase (COX)-1 and -2 pathways. Moreover, 
      BmooMPalpha-I upregulated COX-2 protein expression but not microsomal prostaglandin E 
      synthase-1 (mPGES-1) expression. In addition, we demonstrate that the enzymatic 
      activity of BmooMPalpha-I is essential for the activation of prostanoid synthesis 
      pathways in preadipocytes. These data highlight preadipocytes as important 
      targets for metalloproteinases and provide new insights into the contribution of 
      these enzymes to the inflammation of adipose tissue and tissues adjacent to it.
FAU - Janovits, Priscila Motta
AU  - Janovits PM
AD  - Laboratorio de Farmacologia, Instituto Butantan, Sao Paulo 05503-900, Brazil.
AD  - Centre of Excellence in New Target Discovery (CENTD), Instituto Butantan, Sao 
      Paulo 05503-900, Brazil.
FAU - Leiguez, Elbio
AU  - Leiguez E
AD  - Laboratorio de Farmacologia, Instituto Butantan, Sao Paulo 05503-900, Brazil.
AD  - Centre of Excellence in New Target Discovery (CENTD), Instituto Butantan, Sao 
      Paulo 05503-900, Brazil.
FAU - Portas, Viviane
AU  - Portas V
AD  - Centre of Excellence in New Target Discovery (CENTD), Instituto Butantan, Sao 
      Paulo 05503-900, Brazil.
AD  - Laboratorio de Desenvolvimento e Inovacao, Instituto Butantan, Sao Paulo 
      05503-900, Brazil.
FAU - Teixeira, Catarina
AU  - Teixeira C
AUID- ORCID: 0000-0001-5887-7663
AD  - Laboratorio de Farmacologia, Instituto Butantan, Sao Paulo 05503-900, Brazil.
AD  - Centre of Excellence in New Target Discovery (CENTD), Instituto Butantan, Sao 
      Paulo 05503-900, Brazil.
LA  - eng
GR  - 2015/50040-4/Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210622
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (Crotalid Venoms)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - EC 3.1.1.4 (Group IV Phospholipases A2)
RN  - EC 3.4.24.- (BmooMP-alpha-I, Bothrops moojeni)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/*metabolism
MH  - Animals
MH  - Crotalid Venoms/*pharmacology
MH  - Dinoprostone/*metabolism
MH  - Group IV Phospholipases A2/*metabolism
MH  - Inflammation/chemically induced/metabolism
MH  - Metalloendopeptidases/*pharmacology
MH  - Mice
MH  - Prostaglandin-Endoperoxide Synthases/*metabolism
MH  - Signal Transduction/*drug effects
PMC - PMC8301905
OTO - NOTNLM
OT  - adipokines
OT  - cytokines
OT  - metalloproteinase
OT  - preadipocytes
OT  - prostaglandins
COIS- The authors declare no conflict of interest.
EDAT- 2021/07/03 06:00
MHDA- 2021/09/24 06:00
PMCR- 2021/06/22
CRDT- 2021/07/02 01:27
PHST- 2021/04/02 00:00 [received]
PHST- 2021/06/10 00:00 [revised]
PHST- 2021/06/11 00:00 [accepted]
PHST- 2021/07/02 01:27 [entrez]
PHST- 2021/07/03 06:00 [pubmed]
PHST- 2021/09/24 06:00 [medline]
PHST- 2021/06/22 00:00 [pmc-release]
AID - biom11070921 [pii]
AID - biomolecules-11-00921 [pii]
AID - 10.3390/biom11070921 [doi]
PST - epublish
SO  - Biomolecules. 2021 Jun 22;11(7):921. doi: 10.3390/biom11070921.