2023
DOI: 10.3390/antiox12030692
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Dimethyl Itaconate Inhibits Melanogenesis in B16F10 Cells

Abstract: Itaconate is a metabolite produced to counteract and resolve pro-inflammatory responses when macrophages are challenged with intracellular or extracellular stimuli. In the present study, we have observed that dimethyl itaconate (DMI) inhibits melanogenesis in B16F10 cells. DMI inhibits microphthalmia-associated transcription factor (MITF) and downregulates the expression of MITF target genes, such as tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2). DMI also decr… Show more

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Cited by 4 publications
(5 citation statements)
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“…The PAX3 gene is first expressed in embryonic neural crest precursor cells and plays an important role in the differentiation and migration of melanoblasts into melanocytes during this process [ 24 ]. In addition, TYR is the rate-limiting enzyme for melanin synthesis, which is widely expressed and present in melanocytes [ 25 ]. And MITF regulates the expression of TYR and Karin used immunocytochemical staining of MITF protein to study the mechanism of melanin synthesis in melanocytes [ 26 ], which suggests that MITF is expressed in melanocytes.…”
Section: Discussionmentioning
confidence: 99%
“…The PAX3 gene is first expressed in embryonic neural crest precursor cells and plays an important role in the differentiation and migration of melanoblasts into melanocytes during this process [ 24 ]. In addition, TYR is the rate-limiting enzyme for melanin synthesis, which is widely expressed and present in melanocytes [ 25 ]. And MITF regulates the expression of TYR and Karin used immunocytochemical staining of MITF protein to study the mechanism of melanin synthesis in melanocytes [ 26 ], which suggests that MITF is expressed in melanocytes.…”
Section: Discussionmentioning
confidence: 99%
“…This melanogenic process triggers the activation of the multiplayer transcription factor MITF, which regulates tyrosinase, TRP-1, and TRP-2. Therefore, the blocking of tyrosinase-related signaling pathways prevents the early stages of melanogenesis and benefits the skin-whitening response [ 30 , 31 ]. Previously, hydroquinone, arbutin, and kojic acid were used as inhibitors of melanogenesis for hyperpigmentation.…”
Section: Discussionmentioning
confidence: 99%
“…Macrophages activated via LPS stimulation activate the MAPK signaling pathway, including ERK, p38, and JNK, to produce a variety of proinflammatory cytokines and inflammatory mediators. Therefore, we next performed Western blot experiments to elucidate the involvement of MAPK signaling as a mechanism through which 3,6′-DMC inhibits the inflammatory response of RAW 264.7 cells [ 30 , 31 ]. As shown in Figure 12 , the phosphorylation of ERK, JNK, and p38 by LPS in RAW 264.7 cells was attenuated in the presence of 3,6′-DMC, indicating the ability of 3,6′-DMC to downregulate the production of pro-inflammatory cytokines and inflammatory mediators through the MAPK signaling pathway.…”
Section: Discussionmentioning
confidence: 99%
“…The process is initiated by tyrosinase, which plays a vital role as a rate-limiting enzyme in the early steps of the biosynthesis pathway that produces melanin pigment [11]. Tyrosinase catalyzes the oxidation of tyrosine to 3,4-dihydroxyphenylalanine (DOPA) and dopaquinone, a process regulated by microphthalmia-associated transcription factor (MITF) [12][13][14]. Dopaquinone is naturally oxidized and converted into dopamine [12].…”
Section: Introductionmentioning
confidence: 99%
“…Subsequently, the reaction product dopachrome, which is formed by oxidation and enzymatic reactions, is converted to 5,6dihydroxyindole-2-carboxylic acid (DHICA) by tyrosinase-related protein (TRP)-2, and 2 of 21 dark-colored eumelanin is produced by TRP-1 [11,[15][16][17][18]. In addition to its role in melanin synthesis, MITF is also involved in the survival and differentiation of melanocytes, and MITF upregulation has been identified in melanoma [13,19,20]. Conversely, pale skin in the elderly has been associated with reduced tyrosinase activity and melanogenesis due to aging [21,22].…”
Section: Introductionmentioning
confidence: 99%