PMID- 35807430
OWN - NLM
STAT- MEDLINE
DCOM- 20220712
LR  - 20220720
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 27
IP  - 13
DP  - 2022 Jun 29
TI  - Dimethyl Itaconate Reduces alpha-MSH-Induced Pigmentation via Modulation of AKT and 
      p38 MAPK Signaling Pathways in B16F10 Mouse Melanoma Cells.
LID - 10.3390/molecules27134183 [doi]
LID - 4183
AB  - Dimethyl itaconate (DMI) exhibits an anti-inflammatory effect. Activation of 
      nuclear factor erythroid 2-related factor 2 (NRF2) is implicated in the 
      inhibition of melanogenesis. Therefore, DMI and itaconic acid (ITA), classified 
      as NRF2 activators, have potential uses in hyperpigmentation reduction. The 
      activity of cyclic adenosine monophosphate (cAMP) response element-binding 
      protein (CREB), an important transcription factor for MITF gene promoter, is 
      regulated by glycogen synthase kinase 3beta (GSK3beta) and protein kinase A (PKA). 
      Here, we investigated the inhibitory effect of ITA and DMI on 
      alpha-melanocyte-stimulating hormone (alpha-MSH)-induced MITF expression and the 
      modulatory role of protein kinase B (AKT) and GSK3beta in melanogenesis in B16F10 
      mouse melanoma cells. These cells were incubated with alpha-MSH alone or in 
      combination with ITA or DMI. Proteins were visualized and quantified using 
      immunoblotting and densitometry. Compared to ITA, DMI treatment exhibited a 
      better inhibitory effect on the alpha-MSH-induced expression of melanogenic proteins 
      such as MITF. Our data indicate that DMI exerts its anti-melanogenic effect via 
      modulation of the p38 mitogen-activated protein kinase (MAPK) and AKT signaling 
      pathways. In conclusion, DMI may be an effective therapeutic agent for both 
      inflammation and hyperpigmentation.
FAU - Jang, Sungchan
AU  - Jang S
AUID- ORCID: 0000-0003-0379-4080
AD  - Department of Pharmaceutical Engineering & Biotechnology, Sun Moon University, 
      Asan 31460, Korea.
FAU - Chi, Won-Jae
AU  - Chi WJ
AD  - Microorganism Resources Division, National Institute of Biological Resources, 
      Incheon 17058, Korea.
FAU - Kim, Seung-Young
AU  - Kim SY
AD  - Department of Pharmaceutical Engineering & Biotechnology, Sun Moon University, 
      Asan 31460, Korea.
LA  - eng
PT  - Journal Article
DEP - 20220629
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Melanins)
RN  - 0 (Microphthalmia-Associated Transcription Factor)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Succinates)
RN  - 11JIB0YI93 (dimethyl itaconate)
RN  - 581-05-5 (alpha-MSH)
RN  - EC 1.14.18.1 (Monophenol Monooxygenase)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Glycogen Synthase Kinase 3 beta/metabolism
MH  - *Hyperpigmentation/metabolism
MH  - *MAP Kinase Signaling System/drug effects
MH  - Melanins/metabolism
MH  - *Melanoma, Experimental/drug therapy/metabolism
MH  - Mice
MH  - Microphthalmia-Associated Transcription Factor/genetics/metabolism
MH  - Monophenol Monooxygenase/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - Pigmentation
MH  - *Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction
MH  - Succinates
MH  - alpha-MSH/metabolism/pharmacology
MH  - *p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC9268225
OTO - NOTNLM
OT  - GSK3beta
OT  - MITF
OT  - NRF2
OT  - anti-melanogenic
OT  - dimethyl itaconate
OT  - itaconic acid
COIS- The authors have no conflict of interest.
EDAT- 2022/07/10 06:00
MHDA- 2022/07/14 06:00
PMCR- 2022/06/29
CRDT- 2022/07/09 01:19
PHST- 2022/05/03 00:00 [received]
PHST- 2022/06/21 00:00 [revised]
PHST- 2022/06/27 00:00 [accepted]
PHST- 2022/07/09 01:19 [entrez]
PHST- 2022/07/10 06:00 [pubmed]
PHST- 2022/07/14 06:00 [medline]
PHST- 2022/06/29 00:00 [pmc-release]
AID - molecules27134183 [pii]
AID - molecules-27-04183 [pii]
AID - 10.3390/molecules27134183 [doi]
PST - epublish
SO  - Molecules. 2022 Jun 29;27(13):4183. doi: 10.3390/molecules27134183.