PMID- 38288135
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240131
IS  - 2667-2421 (Electronic)
IS  - 2667-2421 (Linking)
VI  - 16
DP  - 2024 Jun
TI  - Citrullinated isomer of myelin basic protein can induce inflammatory responses in 
      astrocytes.
PG  - 127-134
LID - 10.1016/j.ibneur.2023.12.003 [doi]
AB  - PURPOSE: During the course of demyelinating inflammatory diseases, myelin-derived 
      proteins, including myelin basic protein(MBP), are secreted into extracellular 
      space. MBP shows extensive post-translational modifications, including 
      deimination/citrullination. Deiminated MBP is structurally less ordered, 
      susceptible to proteolytic attack, and more immunogenic than unmodified MBP. This 
      study investigated the effect of the deiminated/citrullinated isomer of MBP(C8) 
      and the unmodified isomer of MBP(C1) on cultured primary astrocytes. METHODS: MBP 
      charge isomers were isolated/purified from bovine brain. Primary astrocyte 
      cultures were prepared from the 2-day-old Wistar rats. For evaluation of 
      glutamate release/uptake a Fluorimetric glutamate assay was used. Expression of 
      peroxisome proliferator-activated receptor-gamma(PPAR-gamma), excitatory amino acid 
      transporter 2(EAAT2), the inhibitor of the nuclear factor kappa-B(ikB) and high 
      mobility group-B1(HMGB1) protein were assayed by Western blot analysis. IL-17A 
      expression was determined in cell medium by ELISA. RESULTS: We found that MBP(C8) 
      and MBP(C1) acted differently on the uptake/release of glutamate in astrocytes: 
      C1 increased glutamate uptake and did not change its release, whereas C8 
      decreased glutamate release but did not change its uptake. Both isomers increased 
      the expression of PPAR-gamma and EAAT2 to the same degree. Western blots of cell 
      lysates revealed decreased expression of ikB and increased expression of HMGB1 
      proteins after treatment of astrocytes by C8. Moreover, C8-treated cells released 
      more nitric oxide and proinflammatory IL-17A than C1-treated cells. CONCLUSIONS: 
      These data suggest that the most immunogenic deiminated isomer C8, in parallel to 
      the decreases in glutamate release, elicits an inflammatory response and enhances 
      the secretion of proinflammatory molecules via activation of nuclear factor kappa 
      B(NF-kB). SUMMARY STATEMENT: The most modified-citrullinated myelin basic protein 
      charge isomer decreases glutamate release, elicits an inflammatory response and 
      enhances the secretion of proinflammatory molecules via activation of nuclear 
      factor kappa B in astrocytes.
CI  - (c) 2024 The Authors.
FAU - Chikviladze, Marika
AU  - Chikviladze M
AD  - Institute of Chemical Biology, Ilia State University, Tbilisi, Georgia.
FAU - Mamulashvili, Nino
AU  - Mamulashvili N
AD  - Institute of Chemical Biology, Ilia State University, Tbilisi, Georgia.
FAU - Sepashvili, Maia
AU  - Sepashvili M
AD  - Institute of Chemical Biology, Ilia State University, Tbilisi, Georgia.
AD  - Department of Biochemistry, I. Beritashvili Center of Experimental Biomedicine, 
      Tbilisi, Georgia.
FAU - Narmania, Nana
AU  - Narmania N
AD  - Institute of Chemical Biology, Ilia State University, Tbilisi, Georgia.
AD  - Department of Biochemistry, I. Beritashvili Center of Experimental Biomedicine, 
      Tbilisi, Georgia.
FAU - Ramsden, Jeremy
AU  - Ramsden J
AD  - Department of Biomedical Research, The University of Buckingham, Hunter Street, 
      Buckingham MK18 1EG, UK.
FAU - Shanshiashvili, Lali
AU  - Shanshiashvili L
AD  - Institute of Chemical Biology, Ilia State University, Tbilisi, Georgia.
AD  - Department of Biochemistry, I. Beritashvili Center of Experimental Biomedicine, 
      Tbilisi, Georgia.
FAU - Mikeladze, David
AU  - Mikeladze D
AD  - Institute of Chemical Biology, Ilia State University, Tbilisi, Georgia.
AD  - Department of Biochemistry, I. Beritashvili Center of Experimental Biomedicine, 
      Tbilisi, Georgia.
LA  - eng
PT  - Journal Article
DEP - 20231219
PL  - Netherlands
TA  - IBRO Neurosci Rep
JT  - IBRO neuroscience reports
JID - 101775148
PMC - PMC10823069
OTO - NOTNLM
OT  - Astrocytes
OT  - Deimination
OT  - Glutamate
OT  - Inflammation
OT  - Myelin basic protein
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2024/01/30 06:42
MHDA- 2024/01/30 06:43
PMCR- 2023/12/19
CRDT- 2024/01/30 03:38
PHST- 2023/07/04 00:00 [received]
PHST- 2023/12/15 00:00 [accepted]
PHST- 2024/01/30 06:43 [medline]
PHST- 2024/01/30 06:42 [pubmed]
PHST- 2024/01/30 03:38 [entrez]
PHST- 2023/12/19 00:00 [pmc-release]
AID - S2667-2421(23)02290-X [pii]
AID - 10.1016/j.ibneur.2023.12.003 [doi]
PST - epublish
SO  - IBRO Neurosci Rep. 2023 Dec 19;16:127-134. doi: 10.1016/j.ibneur.2023.12.003. 
      eCollection 2024 Jun.