Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration

Jhanji, Megha; Rao, Chintada Nageswara; Massey, Jacob C.; Hope, Marion C.; Zhou, Xueyan; Keene, C. Dirk; Ma, Tao; Wyatt, Michael D.; Stewart, Jason A.; Sajish, Mathew

doi:10.1038/s41467-022-30785-8

Cited by 19 publications

(12 citation statements)

References 82 publications

(152 reference statements)

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“…To circumvent this, we opted to apply R daily without disturbing the gauze patch from the treated area of mouse dorsal skin. The R concentration of 2.5 μg/mL was selected based on previous studies [ 2 , 9 ]. This concentration of R is considered moderate and physiologically relevant for in vivo studies as well [ 69 ].…”

Section: Discussionmentioning

confidence: 99%

“…Resveratrol (trans-3-4′,5-trihydroxystilbene, R) is an extensively studied natural polyphenolic phytoalexin enriched in red grapes that has gained attention for its overall anti-inflammatory effects [ 2 , 3 , 4 , 5 , 6 , 7 ]. However, animal studies and human clinical trials have yielded contrasting results with beneficial, lack of beneficial, or even adverse effects on health, owing to differences in experimental models, R bioavailability and pharmacokinetics [ 8 ], dosing [ 9 , 10 ], formulation, and circadian variation [ 2 ]. Additionally, R exerts contrasted effects depending on the prevalent stereoisomer present in solution [ 2 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, animal studies and human clinical trials have yielded contrasting results with beneficial, lack of beneficial, or even adverse effects on health, owing to differences in experimental models, R bioavailability and pharmacokinetics [ 8 ], dosing [ 9 , 10 ], formulation, and circadian variation [ 2 ]. Additionally, R exerts contrasted effects depending on the prevalent stereoisomer present in solution [ 2 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Resveratrol Protects against Skin Inflammation through Inhibition of Mast Cell, Sphingosine Kinase-1, Stat3 and NF-κB p65 Signaling Activation in Mice

Carlucci

Hui

Chumanevich

et al. 2023

IJMS

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Inflammation is pathogenic to skin diseases, including atopic dermatitis (AD) and eczema. Treatment for AD remains mostly symptomatic with newer but costly options, tainted with adverse side effects. There is an unmet need for safe therapeutic and preventative strategies for AD. Resveratrol (R) is a natural compound known for its anti-inflammatory properties. However, animal and human R studies have yielded contrasting results. Mast cells (MCs) are innate immune skin-resident cells that initiate the development of inflammation and progression to overt disease. R’s effects on MCs are also controversial. Using a human-like mouse model of AD development consisting of a single topical application of antigen ovalbumin (O) for 7 days, we previously established that the activation of MCs by a bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) initiated substantial skin remodeling compared to controls. Here, we show that daily R application normalized O-mediated epidermal thickening, ameliorated cell infiltration, and inhibited skin MC activation and chemokine expression. We unraveled R’s multiple mechanisms of action, including decreased activation of the S1P-producing enzyme, sphingosine kinase 1 (SphK1), and of transcription factors Signal Transducer and Activator of Transcription 3 (Stat3) and NF-κBp65, involved in chemokine production. Thus, R may be poised for protection against MC-driven pathogenic skin inflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Resveratrol Protects against Skin Inflammation through Inhibition of Mast Cell, Sphingosine Kinase-1, Stat3 and NF-κB p65 Signaling Activation in Mice

Carlucci

Hui

Chumanevich

et al. 2023

IJMS

Self Cite

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“…Despite the lack of definite evidence, the role of resveratrol on the cerebral blood flow is important especially considering the vascular alterations found in most of the age-related diseases [ 176 ]. Interestingly, recent findings demonstrated that cis- and trans-resveratrol have the opposite effects on histone serine-ADP-ribosylation and tyrosine-induced neurodegeneration, so that the age-associated increase in serum tyrosine levels may affect neurocognitive and metabolic disorders, offering a plausible explanation for divergent results obtained in clinical trials using resveratrol [ 177 ].…”

Section: Oxidative Stressmentioning

confidence: 99%

Antioxidant Intervention to Improve Cognition in the Aging Brain: The Example of Hydroxytyrosol and Resveratrol

Terracina

Petrella

Francati

et al. 2022

IJMS

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Both physiological and pathological aging processes induce brain alterations especially affecting the speed of processing, working memory, conceptual reasoning and executive functions. Many therapeutic approaches to reduce the impact of brain aging on cognitive functioning have been tested; unfortunately, there are no satisfactory results as a single therapy. As aging is partly contributed by free radical reactions, it has been proposed that exogenous antioxidants could have a positive impact on both aging and its associated manifestations. The aim of this report is to provide a summary and a subsequent review of the literature evidence on the role of antioxidants in preventing and improving cognition in the aging brain. Manipulation of endogenous cellular defense mechanisms through nutritional antioxidants or pharmacological compounds represents an innovative approach to therapeutic intervention in diseases causing brain tissue damage, such as neurodegeneration. Coherently with this notion, antioxidants, especially those derived from the Mediterranean diet such as hydroxytyrosol and resveratrol, seem to be able to delay and modulate the cognitive brain aging processes and decrease the occurrence of its effects on the brain. The potential preventive activity of antioxidants should be evaluated in long-term exposure clinical trials, using preparations with high bioavailability, able to bypass the blood-brain barrier limitation, and that are well standardized.

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“…Recently, tyrosine transfer-RNA synthetase (TyrRS), a member of the aminoacyl-tRNA synthetase (AARS) family, was reported to exert a neuroprotective effect on Alzheimer's disease (AD). 6 High expression of TyrRS significantly attenuated oxidative DNA damage in primary rat cortical neurons. 6 Moreover, TyrRS gene mutation was associated with the occurrence of the peripheral nerve degeneration diseases Charcot-Marie-Tooth and Leber hereditary optic neuropathy.…”

mentioning

confidence: 95%

Low-Dose Trans-Resveratrol Ameliorates Diabetes-Induced Retinal Ganglion Cell Degeneration via TyrRS/c-Jun Pathway

Xiao

Zheng

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Purpose The purpose of this study was to investigate the protective effect of low-dose trans- resveratrol ( trans- RSV) on diabetes-induced retinal ganglion cell (RGC) degeneration and its possible mechanism. Methods A streptozotocin-induced diabetic mouse model was established and treated with or without trans -RSV intragastric administration (10 mg/kg body weight/day) for 12 weeks. Oscillatory potentials (Ops) of the dark-adapted electroretinogram (ERG) were recorded. The number of RGCs was detected by Tuj1 and TUNEL staining. The apoptosis markers in the retina were analyzed by Western blot. The cross sections of optic nerves were observed by transmission electron microscopy. In addition, mouse neuroblastoma N2a cells were injured by high-glucose (HG) treatment. Cell viability and apoptosis were measured with or without low-dose trans -RSV treatment. The intracellular localization of tyrosyl transfer-RNA synthetase (TyrRS) was observed in both mouse retinas and N2a cells. The effects of low-dose trans -RSV on the binding of TyrRS to the transcription factor c-Jun and the binding of c-Jun to pro-apoptotic genes were analyzed by co-IP and ChIP assays in HEK 293 cells. Results Trans -RSV relieved electrophysiological injury of retinas and inhibited RGC apoptosis in diabetic mice. It also protected N2a cells from HG-induced apoptosis. Additionally, it promoted TyrRS nuclear translocation in both diabetic mouse retinas and HG-treated N2a cells. Trans -RSV promoted TyrRS binding to c-Jun, inhibited the phosphorylation of Ser-63 of c-Jun, and downregulated pro-apoptotic gene transcription. Conclusions Low-dose trans -RSV can ameliorate diabetes-induced RGC degeneration via the TyrRS/c-Jun pathway. It can promote TyrRS nuclear translocation and bind to c-Jun, downregulating c-Jun phosphorylation and downstream pro-apoptotic genes.

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Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration

Cited by 19 publications

References 82 publications

Resveratrol Protects against Skin Inflammation through Inhibition of Mast Cell, Sphingosine Kinase-1, Stat3 and NF-κB p65 Signaling Activation in Mice

Resveratrol Protects against Skin Inflammation through Inhibition of Mast Cell, Sphingosine Kinase-1, Stat3 and NF-κB p65 Signaling Activation in Mice

Antioxidant Intervention to Improve Cognition in the Aging Brain: The Example of Hydroxytyrosol and Resveratrol

Low-Dose Trans-Resveratrol Ameliorates Diabetes-Induced Retinal Ganglion Cell Degeneration via TyrRS/c-Jun Pathway

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