Differential Induction of Reactive Oxygen Species and Expression of Antioxidant Enzymes in Human Melanocytes Correlate with Melanin Content: Implications on the Response to Solar UV and Melanoma Susceptibility

Upadhyay, Parth Rajendrakumar; Starner, Renny J.; Swope, Viki B.; Wakamatsu, Kazumasa; Ito, Shosuke; Abdel‐Malek, Zalfa

doi:10.3390/antiox11061204

Cited by 16 publications

(7 citation statements)

References 76 publications

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“…Human Chromatophores synthesize two types of melanin, namely, eumelanin (EM) and phaeomelanin (PM). The content of eumelanin is directly related to skin pigmentation and has a photoprotective effect, which can protect the skin from ultraviolet rays, thereby reducing the incidence rate of Melanoma ( Upadhyay et al, 2022 ). Moreover, a high level of plasma glucose is often associated with high BMI and obesity.…”

Section: Discussionmentioning

confidence: 99%

Association between glycemic traits and melanoma: a mendelian randomization analysis

Zhang,

Lu,

et al. 2023

Front. Genet.

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Background: The causation of Glycemic Traits and risks of Melanoma remains unknown. We used Mendelian Randomization (MR) to assess the links between Glycemic Traits and Melanoma.Method: Pooled data from Genome-Wide Association Studies (GWAS) were utilized to examine the relationships that exist between Fasting Insulin (n = 26), 2-h Glucose (n = 10), Fasting Glucose (n = 47), HbA1c (n = 68), and Type-2 Diabetes (n = 105) and Melanoma. We evaluated the correlation of these variations with melanoma risk using Two-Samples MR.Result: In the IVW model, Fasting Glucose (OR = 0.99, 95%CI = 0.993–0.998, p < 0.05, IVW), Type-2 Diabetes (OR = 0.998, 95%CI = 0.998–0.999, p < 0.01, IVW) and HbA1c (OR = 0.19, 95%CI = 0.0415–0.8788, p < 0.05, IVW) was causally associated with a lower risk of Melanoma. In all models analyzed, there was no apparent causal relationship between Fasting Insulin and Melanoma risk. There was no obvious causal difference in the IVW analysis of 2-h Glucose and Melanoma, but its p < 0.05 in MR Egger (OR = 0.99, 95%CI = 0.9883–0.9984, p < 0.05, MR Egger), and the direction was consistent in other MR analyses, suggesting that there may be a causal relationship.Conclusion: The results of this study suggest that a higher risk of Fasting Glucose, Type-2 Diabetes, 2-h Glucose, and HbA1c may be associated with a lower risk of Melanoma. However, no causal relationship between fasting insulin and melanoma was found. These results suggest that pharmacological or lifestyle interventions that regulate plasma glucose levels in the body may be beneficial in the prevention of melanoma.

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Section: Discussionmentioning

confidence: 99%

Association between glycemic traits and melanoma: a mendelian randomization analysis

Zhang,

Lu,

et al. 2023

Front. Genet.

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“…UV contributes to the reduction of antioxidant genes. In human melanocytes and dermal fibroblasts, UV‐B reduced the total and basal antioxidant GSH content (Shin et al, 2018 ; Upadhyay et al, 2022 ). Also, the activity of another antioxidant enzyme, catalase, was reduced to UV light in the model organism (Zhang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

PARP1 inhibition enhances reactive oxygen species on gut microbiota

Zhuang

Wang

Ding

et al. 2022

Journal Cellular Physiology

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Poly(ADP-ribose) polymerase 1 (PARP1) plays a key role in genome stability by modulating DNA-damage responses. Activated by DNA interruptions through ultraviolet (UV) exposure, PARylation is synthesized by PARP1 and serves as a survival mechanism for cancer and metabolic diseases. Several strategies including ROS and antimicrobial peptides (AMPs) function in host defenses, while the targeted tissue and mechanism under DNA damage are unknown. Here, we show that DNA damage induces responses specifically in the gut tissue. The knockdown of PARP1 reduces the activation of PARylation. Parp1 knockdown under DNA damage results in over-accumulated ROS and secretion of AMPs through the regulation of Relish, a subunit of nuclear factor-κB (NF-κB). Double-knockdown of Parp1 and Relish specifically in the gut inhibits AMP secretion. In conclusion, the host defense is achieved through ROS accumulation rather than the AMPs under DNA damage. In contrast, the knockdown of PARP1 exacerbates ROS accumulation to a harmful level. Under this circumstance, NF-κb targeted AMP secretion is provoked for host defense. Microbiome and functional analysis provide evidence for the hazard of DNA damage and show variations in the metabolic pathways following Parp1 inhibition. Our findings suggest the notion that PARP1 inhibition contributes to ROS accumulation under DNA damage and its role in NF-κb activation for host defense.

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“…Ultraviolet (UV) exposure is known to lead to the generation of ROS, resulting in cell death [ 97 , 98 ]. Together with DNA lesions, like cyclobutane-pyrimidine dimers (CPDs), 6-4 photoproducts (6-4PPs) and their Dewar valence isomers [ 99 ], light-induced ROS generation is a major issue when human skin is exposed to solar radiation; this can be partially reduced by naturally extracted melanin [ 100 ].…”

Section: Protection From Radiation Induced Rosmentioning

confidence: 99%

Recent Applications of Melanin-like Nanoparticles as Antioxidant Agents

et al. 2023

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Nanosized antioxidants are highly advantageous in terms of versatility and pharmacokinetics, with respect to conventional molecular ones. Melanin-like materials, artificial species inspired by natural melanin, combine recognized antioxidant (AOX) activity with a unique versatility of preparation and modification. Due to this versatility and documented biocompatibility, artificial melanin has been incorporated into a variety of nanoparticles (NP) in order to give new platforms for nanomedicine with enhanced AOX activity. In this review article, we first discuss the chemical mechanisms behind the AOX activity of materials in the context of the inhibition of the radical chain reaction responsible for the peroxidation of biomolecules. We also focus briefly on the AOX properties of melanin-like NP, considering the effect of parameters such as size, preparation methods and surface functionalization on them. Then, we consider the most recent and relevant applications of AOX melanin-like NPs that are able to counteract ferroptosis and be involved in the treatment of important diseases that affect, e.g., the cardiovascular and nervous systems, as well as the kidneys, liver and articulations. A specific section will be dedicated to cancer treatment, since the role of melanin in this context is still very debated. Finally, we propose future strategies in AOX development for a better chemical understanding of melanin-like materials. In particular, the composition and structure of these materials are still debated, and they present a high level of variability. Thus, a better understanding of the mechanism behind the interaction of melanin-like nanostructures with different radicals and highly reactive species would be highly advantageous for the design of more effective and specific AOX nano-agents.

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Differential Induction of Reactive Oxygen Species and Expression of Antioxidant Enzymes in Human Melanocytes Correlate with Melanin Content: Implications on the Response to Solar UV and Melanoma Susceptibility

Cited by 16 publications

References 76 publications

Association between glycemic traits and melanoma: a mendelian randomization analysis

Association between glycemic traits and melanoma: a mendelian randomization analysis

PARP1 inhibition enhances reactive oxygen species on gut microbiota

Recent Applications of Melanin-like Nanoparticles as Antioxidant Agents

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