Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A systematic exploration reveals the potential of spermidine for hypopigmentation treatment through the stabilization of melanogenesis-associated proteins

ABSTRACT: Spermidine (SPD), a polyamine naturally present in living organisms, is known to prolong lifespan in animals. In this study, the role of SPD in melanogenesis were investigated and showed the possibility as a pigmenting agent. SPD treatment increased melanin production in melanocytes in a dose dependent manner. Computational analysis with RNA-sequencing data revealed the alteration of protein degradation by SPD treatment without changing the expressions of melanogenesis-related genes. Indeed, SPD treatment significantly increased the stabilities of tyrosinase-related protein (TRP)-1 and -2 while inhibiting ubiquitination, which was confirmed by treatment of proteasome inhibitor MG132. Inhibition of protein synthesis by cycloheximide (CHX) showed that SPD treatment increased the resistance of TRP-1 and TRP-2 to protein degradation. To identify the proteins involved in SPD transportation in melanocytes, the expression of several solute carrier (SLC) membrane transporters was assessed and, among 27 transporter genes, SLC3A2, SLC7A1, SLC18B1, and SLC22A18 were highly expressed, implying they are putative SPD transporters in melanocytes. Furthermore, SLC7A1 and SLC22A18 were downregulated by SPD treatment, indicating their active involvement in polyamine homeostasis. Finally, we applied SPD to a human skin equivalent and observed elevated melanin production. Our results identify SPD as a potential natural product to alleviate hypopigmentation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE209538 | GEO | 2022/07/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Translational Autoregulation of the S. cerevisiae High-affinity Polyamine Transporter Hol1

Project description:Study is aimed to understand translation regulation of mRNA in low and high polyamines in S. cerevisiae. mRNA seq and Ribosome profiling were performed in yeast cells, in duplicates, under low (0 spermidine) and high (10 µM) spermidine. Translation efficiency was calculated (low vs high SPD) and GO analysis reveals 23 transporters as the only class undergo TE downregulation in high SPD condition. Further, we investigated role of these 23 transporters in polyamine transport and identified HOL1 as the high affinity polyamine transporter. This study further show that HOL1 is under polyamine control of translation regulation through conserved fungal uORF MLLLPS*.

2021-08-09 | GSE171392 | GEO

Small molecule ML233 is a direct inhibitor of tyrosinase function and reduces melanoma proliferation

Project description:Melanogenesis is the biological process regulating the synthesis of melanin pigments in melanocytes. Defective melanogenesis is associated with numerous human skin diseases, including, but not limited to, albinism, vitiligo, melasma, hypo- and hyperpigmentation disorders. Tyrosinase is the rate-limiting enzyme controlling melanogenesis, and hence tremendous efforts have been made to identify potent and safe inhibitors of tyrosinase function. Such inhibitors would also have potential as cancer therapies; melanomas are derived via malignant transformation of melanocytes, and inhibition of tyrosinase activity and/or melanogenesis has been suggested as a possible therapeutic strategy. However, despite decades of research, there is currently no effective treatment that inhibits melanogenesis or tyrosinase activity with no adverse side effects. In this study, we report characterization of the ML233 chemical as a potent inhibitor of tyrosinase activity in vivo and in vitro. We demonstrated that ML233 reduces melanin production in the zebrafish model with no observable significant toxic side effects, and in murine melanoma cells. We also showed that these effects are likely mediated through direct tyrosinase-ML233 interaction, i.e., binding of the ML233 molecule to the active site of the protein to inhibit its function. In addition, we showed that ML233 has the capacity to limit melanoma-cell proliferation in patient-derived xenograft organoids. Together, our results reveal that ML233 plays a dual role via inhibition of both melanin production and melanoma proliferation, and that ML233-mediated tyrosinase inhibition is a potentially safe and effective approach to alleviate the symptoms of melanocyte-associated diseases and thereby substantially improve human health.

2024-05-22 | GSE268076 | GEO

Expression data of primary melanocytes from aryl hydrocarbon deficient mice and corresponding wild-type C57BL/6 mice

Project description:[original Title] Comparison of expression data of primary murine melanocytes from aryl hydrocarbon deficient mice and corresponding wild-type C57BL/6 mice Melanin is produced exclusively by melanocytes and melanogenesis is the vital response to protect skin cells against Ultraviolet B (UVB)-induced DNA damage. The aryl hydrocarbon receptor (AhR) is a transcription factor, which may be involved in the physiological tanning response. Normal murine melanocytes express functional AhR. We tested gene expression in WT versus AhR-deficient mice primary murine melanocytes, isolated from the skin and cultivated for several passages. Skin epidermal cells from 2 individual C57BL/6 mice and 2 individual AhR-deficient mice (deletion of exon2, AhRtm1Bra) were grown for 6-8 weeks in selection medium to propagate melanocytes.

2010-09-05 | E-GEOD-19411 | biostudies-arrayexpress

Expression data of primary melanocytes from aryl hydrocarbon deficient mice and corresponding wild-type C57BL/6 mice

2010-09-05 | GSE19411 | GEO

Spermidine augments salt stress resilience in rice roots potentially by enhancing OsbZIP73’s RNA binding capacity

Project description:Background: Rice is a staple crop for over half of the global population, but soil salinization poses a significant threat to its production. As a type of polyamine, spermidine (Spd) has been shown to reduce stress-induced damage in plants, but its specific role and mechanism in protecting rice roots under salt stress require further investigation. Results: This study suggested spermidine (Spd) mitigates salt stress on rice root growth by enhancing antioxidant enzyme activity and reducing peroxide levels. Transcriptomic analysis showed that salt stress caused 333 genes to be upregulated and 1,765 to be downregulated. However, adding Spd during salt treatment significantly altered this pattern: 2,298 genes were upregulated and 844 were downregulated, which indicated Spd reverses some transcriptional changes caused by salt stress. KEGG pathway analysis suggested that Spd influenced key signaling pathways, including MAPK signaling, plant hormone signal transduction, and phenylalanine metabolism. Additionally, the bZIP transcription factor OsbZIP73 was upregulated after Spd treatment, which is confirmed by Western blot. Further insights into the interaction between OsbZIP73 and Spd were gained through fluorescence polarization experiments, showing that Spd enhances protein OsbZIP73's affinity for RNA. Functional enrichment analyses revealed that OsPYL1, OsSPARK1, and various SAUR family genes involved in Spd-affected pathways. The presence of G/A/C-box elements in these genes suggests they are potential targets for OsbZIP73. Conclusions: Our findings suggest a strategy of using spermidine as a chemical alleviator for salt stress and provide insights into the regulatory function of OsbZIP73 in mitigating salt stress in rice roots.

2024-08-01 | GSE189665 | GEO

Ssc-miR-221-3p regulates melanin production in Xiang pigs melanocytes by targeting the TYRP1 gene

Project description:The TYRP1 gene can affect melanogenesis in melanocytes of the Xiang pigs, and ssc-miR-221-3p targets the TYRP1 gene to affect melanogenesis in melanocytes of the Xiang pigs.

2022-11-30 | GSE218870 | GEO

Deficiency in nucleotide excision repair (NER) family gene activity, especially ERCC3, is associated with non-pigmented hair fiber growth

Project description:The hair follicle bulb is the only site of pigment production for the hair shaft and melanogenically active melanocytes are located in the upper hair matrix. We conducted a microarray study to discover gene expression patterns that may be implicated in the lack of melanogenesis in gray hair follicles (HF). Pigmented and non-pigmented HFs collected from the same individuals were micro-dissected into the lower one third including the hair bulb (HB) and the upper hair shaft and sheaths (HS) including the bulge region. Microarray data was verified with qPCR and immunohistochemistry. Target effects were evaluated in vitro on human epidermal melanocytes (HEMs). In comparison to pigmented HS and HBs, several nucleotide excision repair (NER) family genes exhibited statistically significant lower expression both in non-pigmented HS and non-pigmented HB. These genes were identified as ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, ERCC6, XPA, NTPBP, HCNP, DDB2 and POLH. Immunohistochemistry showed consistent results. By siRNA interference we also detected that a deficiency in ERCC3 in melanocytes reduced the ability to produce melanin in vitro. Our results suggest that loss of NER gene function may lead to DNA damage and mutation accumulation in melanocytes, which may possibly lead to cell death. Further, a loss of ERCC3 function may lead to reduced gene transcription and this in turn may lead to reduced melanin production ability. These results offer a new insight into the molecular changes that occur in non-pigmented HF and may also provide novel information with regard to melanogenesis and its regulation.

2010-10-18 | GSE24009 | GEO

Aberrant expression of the DCT gene is implicated in the hyperpigmentation of the visceral peritoneum of the chicken

Project description:Hyperpigmentation of the visceral peritoneum (HVP) has recently garnered significant attention within the poultry industry due to its potential implications for the health of afflicted animals and its adverse effects on the appearance of commercial chicken carcasses. Unfortunately, the heritable characteristics of HVP are not yet fully understood. Motivated by poultry industry demand, we deployed multi-omics comparing the clinical HVP and normal samples profiling the potential regulating molecular landscape in cell and genome resolution, specifically, aiming to decipher the precise molecular genomic marker. Specifically, we identified the signature genes for the HVP phenotype and found that the signature gene of melanogenesis strongly enriched in the HVP group. At the melanocyte level, overexpression of the DCT gene can promote the proliferation of melanocytes, with exogenous Tyr addition. On the contrary, significantly lower melanin content in the supernatant of cells was detected after siRNA interference relative to untreated cells. Through single-cell sequencing, the hyperexpression of melanogenesis-associated genes in melanocytes was echoed. In summary, molecular features of the HVP phenotype were systematically revealed, which may partially explain the strong heterogeneities of the peritoneum phenotype. The hyperpigmentation of the peritoneum is attributed to an excess deposition of melanin, where the DCT hyperexpression can be regarded as a molecular marker related to the deposition of peritoneal melanin. Future directions should deploy gene editing technology to alert the gene expression of DCT to change the phenotype of pigmentation in the visceral peritoneum.

2024-01-01 | GSE246996 | GEO

Keap1 knockdown in melanocytes induces cell proliferation and survival via HO-1-associated β-catenin signaling

Project description:Nrf2-Keap1 signaling pathway protects cells against photo-oxidative stress. Yet in recent works, its role in melanogenesis together with cell protection functions against oxidative stress has been gaining interest. However, its effect on melanogenesis still has contradictory results from different studies. The aims of our study were to investigate the effect of Keap1 silencing in melanocyte on melanogenesis and its associated mechanism. Primary human epidermal melanocytes and melan-a cell line were used for this experiment. RNA sequencing was done to identify genes involved in melanocyte biology using Keap1 knockdown through siRNA techniques. And melanogenesis and the expression of melanogenesis-associated molecules were evaluated in Keap1 silenced melanocyte to examine the effects of Keap1 on melanogenesis, melanocyte growth, and related pathways. RNA-sequencing data revealed that Keap1 knockdown in primary human epidermal melanocytes (PHEMs) induced cell survival-related gene expression. Additionally, siRNA-mediated inhibition of Keap1 led to upregulation of MITF and melanogenesis-associated molecules along with Nrf2 activation in PHEMs. HO-1, a major gene that is upregulated in RNA-sequencing using Keap1-silenced PHEMs, protected melanocytes against H2O2-induced cell death and upregulated MITF and β-catenin expression. Further, increased expression of melanogenesis-associated molecules after Keap1 silencing was validated to occur through HO-1-associated β-catenin activation in a Keap1 and HO-1 double knockdown experiment. This work suggests that Keap1 silencing in melanocytes induced melanogenesis and the expression of melanogenesis-associated molecules through HO-1-associated β-catenin activation. Keap1 downregulation in melanocytes is important for cell proliferation and survival.

2018-01-20 | GSE93895 | GEO

RNA sequencing of particulate metter treated melanocytes

Project description:Purpose: Determine the mechanism of particulate matter-induced signaling in melanocytes. Method: Primary human epidermal melanocytes were treated with particulate matter (5 μg/cm2) and incubated for 24 h. Total RNA (1 ug) from melanocytes were extracted and subjected to library synthesis. Results: Particulate matter-treated melanocytes exhibited upregulation of ER stress, unfolded protein response, and melanogenesis-related molecules. Conclusion: Particulate matter-induced melanocyte signaling was well evaluated using RNA sequencing.

2021-08-19 | GSE165333 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data