PMID- 36902422
OWN - NLM
STAT- MEDLINE
DCOM- 20230315
LR  - 20230315
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 5
DP  - 2023 Mar 5
TI  - Dual Role of Mitogen-Activated Protein Kinase 8 Interacting Protein-1 in 
      Inflammasome and Pancreatic beta-Cell Function.
LID - 10.3390/ijms24054990 [doi]
LID - 4990
AB  - Inflammasomes have been implicated in the pathogenesis of type 2 diabetes (T2D). 
      However, their expression and functional importance in pancreatic beta-cells remain 
      largely unknown. Mitogen-activated protein kinase 8 interacting protein-1 
      (MAPK8IP1) is a scaffold protein that regulates JNK signaling and is involved in 
      various cellular processes. The precise role of MAPK8IP1 in inflammasome 
      activation in beta-cells has not been defined. To address this gap in knowledge, we 
      performed a set of bioinformatics, molecular, and functional experiments in human 
      islets and INS-1 (832/13) cells. Using RNA-seq expression data, we mapped the 
      expression pattern of proinflammatory and inflammasome-related genes (IRGs) in 
      human pancreatic islets. Expression of MAPK8IP1 in human islets was found to 
      correlate positively with key IRGs, including the NOD-like receptor (NLR) family 
      pyrin domain containing 3 (NLRP3), Gasdermin D (GSDMD) and Apoptosis-associated 
      speck-like protein containing a CARD (ASC), but correlate inversely with Nuclear 
      factor kappa beta1 (NF-kappabeta1), Caspase-1 (CASP-1), Interleukin-18 (IL-18), 
      Interleukin-1beta (IL-1beta) and Interleukin 6 (IL-6). Ablation of Mapk8ip1 by siRNA in 
      INS-1 cells down-regulated the basal expression levels of Nlrp3, NLR family CARD 
      domain containing 4 (Nlrc4), NLR family CARD domain containing 1 (Nlrp1), Casp1, 
      Gsdmd, Il-1beta, Il-18, Il-6, Asc, and Nf-kappabeta1 at the mRNA and/or protein level and 
      decreased palmitic acid (PA)-induced inflammasome activation. Furthermore, 
      Mapk8ip1-silened cells substantially reduced reactive oxygen species (ROS) 
      generation and apoptosis in palmitic acid-stressed INS-1 cells. Nonetheless, 
      silencing of Mapk8ip1 failed to preserve beta-cell function against inflammasome 
      response. Taken together, these findings suggest that MAPK8IP1 is involved in 
      regulating beta-cells by multiple pathways.
FAU - Saeed, Rania
AU  - Saeed R
AD  - Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams 
      University, Cairo 11566, Egypt.
AD  - Sharjah Institute for Medical Research, University of Sharjah, Sharjah P.O. Box 
      27272, United Arab Emirates.
FAU - Mohammed, Abdul Khader
AU  - Mohammed AK
AUID- ORCID: 0000-0002-8774-0014
AD  - Sharjah Institute for Medical Research, University of Sharjah, Sharjah P.O. Box 
      27272, United Arab Emirates.
FAU - Saleh, Sarra E
AU  - Saleh SE
AUID- ORCID: 0000-0002-4809-4451
AD  - Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams 
      University, Cairo 11566, Egypt.
FAU - Aboulwafa, Mohammad M
AU  - Aboulwafa MM
AD  - Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams 
      University, Cairo 11566, Egypt.
AD  - Faculty of Pharmacy, King Salman International University, Ras-Sudr, El Tor 
      8701301, Egypt.
FAU - Aboshanab, Khaled M
AU  - Aboshanab KM
AUID- ORCID: 0000-0002-7608-850X
AD  - Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams 
      University, Cairo 11566, Egypt.
FAU - Taneera, Jalal
AU  - Taneera J
AUID- ORCID: 0000-0002-3341-1063
AD  - Sharjah Institute for Medical Research, University of Sharjah, Sharjah P.O. Box 
      27272, United Arab Emirates.
AD  - Department of Basic Sciences, College of Medicine, University of Sharjah, Sharjah 
      P.O. Box 27272, United Arab Emirates.
LA  - eng
GR  - 22010901106 and 2001090176/University of Sharjah, UAE/
PT  - Journal Article
DEP - 20230305
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - EC 3.4.22.36 (Caspase 1)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (NLR Proteins)
RN  - 2V16EO95H1 (Palmitic Acid)
RN  - 0 (Mapk8ip1 protein, rat)
RN  - 0 (MAPK8IP1 protein, human)
RN  - 0 (Adaptor Proteins, Signal Transducing)
SB  - IM
MH  - Humans
MH  - Caspase 1/metabolism
MH  - *Diabetes Mellitus, Type 2
MH  - *Inflammasomes/metabolism
MH  - Interleukin-18
MH  - Interleukin-1beta/metabolism
MH  - Interleukin-6
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - NLR Proteins
MH  - Palmitic Acid
MH  - Adaptor Proteins, Signal Transducing/genetics
MH  - *Insulin-Secreting Cells/metabolism
PMC - PMC10002854
OTO - NOTNLM
OT  - MAPK8IP1
OT  - inflammasome
OT  - pancreatic beta-cell function
OT  - regulation
OT  - siRNA silencing
OT  - type 2 diabetes
COIS- The authors declare no conflict of interest.
EDAT- 2023/03/12 06:00
MHDA- 2023/03/15 06:00
PMCR- 2023/03/05
CRDT- 2023/03/11 01:19
PHST- 2023/01/21 00:00 [received]
PHST- 2023/03/01 00:00 [revised]
PHST- 2023/03/02 00:00 [accepted]
PHST- 2023/03/11 01:19 [entrez]
PHST- 2023/03/12 06:00 [pubmed]
PHST- 2023/03/15 06:00 [medline]
PHST- 2023/03/05 00:00 [pmc-release]
AID - ijms24054990 [pii]
AID - ijms-24-04990 [pii]
AID - 10.3390/ijms24054990 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Mar 5;24(5):4990. doi: 10.3390/ijms24054990.