MHY1485 ameliorates UV-induced skin cell damages via activating mTOR-Nrf2 signaling

Yang, Bo; Xu, Qiuyun; Guo, Chunyan; Huang, Jinwen; Wang, Shumei; Li, Yongmei; Tu, Ying; Zhang, Bi; Ji, Chao; Cheng, Bo

doi:10.18632/oncotarget.14299

Cited by 9 publications

(9 citation statements)

References 37 publications

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“…The mTOR pathway regulates cell growth, proliferation and death by responding to a variety of environmental stimuli, such as nutrients and energy ( 15 ). MHY1485 exerts protective effects on cell death induced by dexamethasone and ultra violet (UV) radiation ( 16 17 ). IL-3, together with stem cell factor, is an essential growth factor to maintain mast cell survival and proliferation ( 1 ).…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Mast Cell Function and Proliferation by mTOR Activator MHY1485

2018

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Mast cells integrate innate and adaptive immunity and are implicated in pathophysiological conditions, including allergy, asthma, and anaphylaxis. Cross-linking of the high-affinity IgE receptor (FcεRI) initiates diverse signal transduction pathways and induces release of proinflammatory mediators by mast cells. In this study, we demonstrated that hyperactivation of mechanistic target of rapamycin (mTOR) signaling using the mTOR activator MHY1485 suppresses FcεRI-mediated mast cell degranulation and cytokine secretion. MHY1485 treatment increased ribosomal protein S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation, which are downstream targets of mTOR complex 1 (mTORC1), but decreased phosphorylation of Akt on mTOR complex 2 (mTORC2) target site serine 473. In addition, this activator decreased β-hexosaminidase, IL-6, and tumor necrosis factor α (TNF-α) release in murine bone marrow-derived mast cells (BMMCs) after FcεRI stimulation. Furthermore, MHY1485-treated BMMCs showed significantly decreased proliferation when cultured with IL-3. These findings suggested hyperactivation of mTORC1 as a therapeutic strategy for mast cell-related diseases.

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Section: Resultsmentioning

confidence: 99%

Inhibition of Mast Cell Function and Proliferation by mTOR Activator MHY1485

2018

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“…In contrast, it was shown that UVB-induced damage is mediated almost solely by ROS generation in the skin [30, 31]. In addition, several publications reported that UV radiation can be attenuated by activating the Nrf2 signaling pathway [32-36]. Thus, the possible effect of SK-119 on UVB-mediated oxidative stress and damage in human skin explants was investigated.…”

Section: Resultsmentioning

confidence: 99%

Nrf2 Activation by SK-119 Attenuates Oxidative Stress, UVB, and LPS-Induced Damage

Kahremany

Babaev

Gvirtz

et al. 2019

Skin Pharmacol Physiol

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Background/Aims: The Nrf2 signaling pathway plays a pivotal role in neutralizing excess reactive oxygen species formation and therefore enhancing the endogenous cellular protection mechanism. Thus, activating this pathway may provide therapeutic options against oxidative stress-related disorders. We have recently applied a computer-aided drug design approach to the design and synthesis of novel Nrf2 enhancers. The current study was aimed at investigating the potential beneficial impact of (E)-5-oxo-1-(4-((2,4,6-trihydroxybenzylidene)amino)phenyl)pyrrolidine-3-carboxylic acid (SK-119) in skin oxidative damage models. Methods: SK-119, tested initially in PC-12 cells, attenuated oxidative stress-induced cytotoxicity concomitantly with Nrf2 activation. The potential impact of this compound was evaluated in skin-based disease models both in vitro (HaCaT cells) and ex vivo (human skin organ culture). Results: The data clearly showed the marked anti-inflammatory and photoprotection properties of the compound; SK-119-treated cells or tissues displayed a reduction in cytokine secretion induced by lipopolysaccharides (LPS) in a manner comparable with dexamethasone. In addition, topical application of SK-119 was able to block UVB-induced oxidative stress and attenuated caspase-mediated apoptosis, DNA adduct formation, and the concomitant cellular damage. Conclusion: These results indicate that SK-119 is an Nrf2 activator that can be used as a prototype molecule for the development of novel treatments of dermatological disorders related to oxidative stress.

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“…UV radiation can lead to oxidative stress in the keratinocytes of the skin and it activates several signaling pathways. On exposure to UV radiation, the generation of ROS increases in the keratinocytes [ 49 , 50 ]. In our experiments, the large extent of oxidative stress caused by UVB radiation led to severe cell damage.…”

Section: Discussionmentioning

confidence: 99%

Formulation of Creams Containing Spirulina Platensis Powder with Different Nonionic Surfactants for the Treatment of Acne Vulgaris

et al. 2020

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Natural products used in the treatment of acne vulgaris may be promising alternative therapies with fewer side effects and without antibiotic resistance. The objective of this study was to formulate creams containing Spirulina (Arthrospira) platensis to be used in acne therapy. Spirulina platensis belongs to the group of micro algae and contains valuable active ingredients. The aim was to select the appropriate nonionic surfactants for the formulations in order to enhance the diffusion of the active substance and to certify the antioxidant and antibacterial activity of Spirulina platensis-containing creams. Lyophilized Spirulina platensis powder (SPP) was dissolved in Transcutol HP (TC) and different types of nonionic surfactants (Polysorbate 60 (P60), Cremophor A6:A25 (CR) (1:1), Tefose 63 (TFS), or sucrose ester SP 70 (SP70)) were incorporated in creams as emulsifying agents. The drug release was evaluated by the Franz diffusion method and biocompatibility was tested on HaCaT cells. In vitro antioxidant assays were also performed, and superoxide dismutase (SOD) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays were executed. Antimicrobial activities of the selected compositions were checked against Staphylococcus aureus (S. aureus) and Cutibacteriumacnes (C. acnes) (formerly Propionibacterium acnes) with the broth microdilution method. Formulations containing SP 70 surfactant with TC showed the most favorable dissolution profiles and were found to be nontoxic. This composition also showed significant increase in free radical scavenger activity compared to the blank sample and the highest SOD enzyme activity was also detected after treatment with the cream samples. In antibacterial studies, significant differences were observed between the treated and control groups after an incubation time of 6 h.

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MHY1485 ameliorates UV-induced skin cell damages via activating mTOR-Nrf2 signaling

Cited by 9 publications

References 37 publications

Inhibition of Mast Cell Function and Proliferation by mTOR Activator MHY1485

Inhibition of Mast Cell Function and Proliferation by mTOR Activator MHY1485

Nrf2 Activation by SK-119 Attenuates Oxidative Stress, UVB, and LPS-Induced Damage

Formulation of Creams Containing Spirulina Platensis Powder with Different Nonionic Surfactants for the Treatment of Acne Vulgaris

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