Diazepam enhances melanogenesis, melanocyte dendricity and melanosome transport via the PBR/cAMP/PKA pathway

Lv, Jinpeng; Fu, Ying; Gao, Rongyin; Li, Jiawen; Kang, Maofan; Song, Guoqiang; Yun, Changjun

doi:10.1016/j.biocel.2019.105620

Cited by 18 publications

(16 citation statements)

References 26 publications

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“…Cell viability was determined via the MTT assay . Briefly, the cells were treated with different concentrations of ISL for 48 hours.…”

Section: Methodsmentioning

confidence: 99%

“…Microphthalmia‐associated transcription factor (MITF) controls melanogenesis through the regulation of the tyrosinase, TRP‐1 and DCT expression and melanosome transport via the regulation of the Rab27a and Cdc42 expression . Activation of PKA promotes pigmentation through CREB‐mediated MITF expression . Mitogen‐activated protein kinases (MAPKs), including extracellular signal‐regulated protein kinase (ERK), p38 and c‐jun N‐terminal kinase (JNK), play important roles in melanogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Isoliquiritigenin inhibits melanogenesis, melanocyte dendricity and melanosome transport by regulating ERK‐mediated MITF degradation

Cao

et al. 2019

Experimental Dermatology

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Isoliquiritigenin (ISL), a flavonoid component from the hydrolysis products of licorice root. It has been reported that ISL inhibited melanogenesis by suppressing the tyrosinase activity in human melanocytes. Recently, ISL was found to induce melanin degradation in human epidermal keratinocytes. However, the role of ISL in pigmentation is not fully understood. In the current study, we aimed to investigate the effects of ISL on pigmentation, and further explored the underlying mechanism. Our results suggested that ISL suppressed basal and α‐MSH‐, ACTH‐ and UV‐induced melanin synthesis, in addition to inhibiting melanocyte dendricity and melanosome transport. ISL played these roles mainly by activating the extracellular signal‐regulated protein kinase pathway. Once activated, it induced microphthalmia‐associated transcription factor degradation and decreased the expression of tyrosinase, TRP‐1, DCT, Rab27a and Cdc42, finally inhibited melanogenesis, melanocyte dendricity and melanosome transport. Our findings suggested that ISL exhibited no cytotoxicity in our research, it may prove quite useful as a safer natural skin‐whitening agent.

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“…Cell viability was determined via the MTT assay . Briefly, the cells were treated with different concentrations of ISL for 48 hours.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Isoliquiritigenin inhibits melanogenesis, melanocyte dendricity and melanosome transport by regulating ERK‐mediated MITF degradation

Cao

et al. 2019

Experimental Dermatology

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“…The present studies showed that FGIN-1-27 suppressed basal, α-MSH, and ET-1-induced MITF expression increase (Figure 3). As mentioned above, FGIN-1-27 inhibiting melanogenesis by decreasing the expression of MITF, tyrosinase, TRP-1, TRP-2 and inhibiting the tyrosinase activity, which is contradictory with previous studies that suggested MDR activation can increase melanogenesis (Lv et al, 2019). There are two possible explanations for this effect.…”

Section: Discussionmentioning

confidence: 71%

“…Mitochondrial diazepam binding inhibitor receptor (MDR) plays a central role in the regulation of lipid and steroid synthesis and is widely distributed in peripheral tissues including skin (Alho et al, 1993). In our previous studies, diazepam, one MDR agonist, regulated pigmentation via the PKA/CREB pathway (Lv et al, 2019). Furthermore, recent findings suggested that MDR activation slightly increased the number of new melanocytes in zebrafish (Allen et al, 2020).…”

Section: Introductionmentioning

confidence: 97%

FGIN-1-27 Inhibits Melanogenesis by Regulating Protein Kinase A/cAMP-Responsive Element-Binding, Protein Kinase C-β, and Mitogen-Activated Protein Kinase Pathways

Jiang

Yang

et al. 2020

Front. Pharmacol.

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FGIN-1-27 is a synthetic mitochondrial diazepam binding inhibitor receptor (MDR) agonist that has demonstrated pro-apoptotic, anti-anxiety, and steroidogenic activity in various studies. Here we report, for the first time, the anti-melanogenic efficacy of FGIN-1-27 in vitro and in vivo. FGIN-1-27 significantly inhibited basal and α-melanocyte-stimulating hormone (α-MSH)-, 1-Oleoyl-2-acetyl-sn-glycerol (OAG)- and Endothelin-1 (ET-1)-induced melanogenesis without cellular toxicity. Mushroom tyrosinase activity assay showed that FGIN-1-27 did not directly inhibit tyrosinase activity, which suggested that FGIN-1-27 was not a direct inhibitor of tyrosinase. Although it was not capable of modulating the catalytic activity of mushroom tyrosinase in vitro, FGIN-1-27 downregulated the expression levels of key proteins that function in melanogenesis. FGIN-1-27 played these functions mainly by suppressing the PKA/CREB, PKC-β, and MAPK pathways. Once inactivated, it decreased the expression of MITF, tyrosinase, TRP-1, TRP-2, and inhibited the tyrosinase activity, finally inhibiting melanogenesis. During in vivo experiments, FGIN-1-27 inhibited the body pigmentation of zebrafish and reduced UVB-induced hyperpigmentation in guinea pig skin, but not a reduction of numbers of melanocytes. Our findings indicated that FGIN-1-27 exhibited no cytotoxicity and inhibited melanogenesis in both in vitro and in vivo models. It may prove quite useful as a safer skin-whitening agent.

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“…The cells were cultured in Dulbecco's modified Eagle's medium (DMEM) (Gibco, USA) supplemented with 10% fetal bovine serum (FBS) (HyClone, USA) at 37°C and 5% CO 2 . Human epidermal melanocytes (HNM) were obtained from Sciencell Research Laboratories (CA, USA) and incubated in 254CF medium (Gibco, USA) containing human melanocyte growth supplement at 37°C and 5% CO 2 (Lv et al, 2019).…”

Section: Cell Culturementioning

confidence: 99%

Protoporphyrin IX Stimulates Melanogenesis, Melanocyte Dendricity, and Melanosome Transport Through the cGMP/PKG Pathway

An²,

Jiang

et al. 2020

Front. Pharmacol.

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Protoporphyrin IX (PPIX) is a heterocyclic organic compound that is the last intermediate in the heme biosynthetic pathway. PPIX, due to its photodynamic effects, is utilized in the treatment of skin diseases. Furthermore, PPIX has been utilized as a melanogenesisstimulating agent in various studies. However, the exact function and mechanism underlying PPIX action in melanocytes remain to be elucidated. In the present study, we sought to further investigate how PPIX affects melanocyte melanogenesis, and whether PPIX is involved in melanin transport. Our findings demonstrated that PPIX increased melanocyte dendricity and melanosome transport, in addition to increasing melanogenesis. PPIX functions primarily by activating the guanylate cyclase (GC) and cyclic guanosine 3', 5'-monophosphate/protein kinase G (cGMP/PKG) signaling pathways. Once activated, these pathways increase tyrosinase activity and the expression of microphthalmiaassociated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 and-2 (TRP-1 and TRP-2), myosin Va, melanophinin, Ras-related protein Rab-27A (Rab27a), and cell division cycle 42 (Cdc42), promoting melanogenesis, melanocyte dendricity, and melanosome transport. Furthermore, the melanogenic effects of PPIX were confirmed in vivo in a zebrafish model system. Our results indicate that PPIX is not cytotoxic and may, thus, be utilized as a pigmentation enhancer.

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Diazepam enhances melanogenesis, melanocyte dendricity and melanosome transport via the PBR/cAMP/PKA pathway

Cited by 18 publications

References 26 publications

Isoliquiritigenin inhibits melanogenesis, melanocyte dendricity and melanosome transport by regulating ERK‐mediated MITF degradation

Isoliquiritigenin inhibits melanogenesis, melanocyte dendricity and melanosome transport by regulating ERK‐mediated MITF degradation

FGIN-1-27 Inhibits Melanogenesis by Regulating Protein Kinase A/cAMP-Responsive Element-Binding, Protein Kinase C-β, and Mitogen-Activated Protein Kinase Pathways

Protoporphyrin IX Stimulates Melanogenesis, Melanocyte Dendricity, and Melanosome Transport Through the cGMP/PKG Pathway

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