Revisiting the role of melatonin in human melanocyte physiology: A skin context perspective

Journal of Pineal Research, Journal Year: 2022, Volume and Issue: 72(3)

Published: Feb. 8, 2022

The evolutionarily ancient methoxyindoleamine, melatonin, has long perplexed investigators by its versatility of functions and mechanisms action, which include the regulation vertebrate pigmentation. Although first discovered through potent skin-lightening effects in amphibians, melatonin's role human skin hair follicle pigmentation impact on melanocyte physiology remain unclear. Synthesizing our limited current understanding this role, we specifically examine melanogenesis, oxidative biology, mitochondrial function, senescence, pigmentation-related clock gene activity, with emphasis skin, yet without ignoring instructive pointers from nonhuman species. Given strict dependence epithelial microenvironment, underscore that responses to melatonin are best interrogated a physiological tissue context. Current evidence suggests some metabolites inhibit both, melanogenesis (via reducing tyrosinase activity) proliferation stimulating membrane receptors (MT1, MT2). We discuss whether putative melanogenesis-inhibitory may occur via activation Nrf2-mediated PI3K/AKT signaling, estrogen receptor-mediated and/or melanocortin-1 receptor- cAMP-dependent melatonin-regulated changes peripheral genes regulate namely Bmal1 Per1. Melatonin also accumulate melanocytes where they exert net cyto- senescence-protective as well antioxidative operating free radical scavengers, synthesis activity ROS scavenging enzymes other antioxidants, promoting DNA repair, enhancing function. argue it is clinically biologically important definitively clarify cell culture-based observations translate into melatonin-induced pigmentary context, is, epidermis follicles ex vivo, confirmed clinical trial results. After defining major open questions field, close suggesting how begin answering them relevant, currently available preclinical situ research models.

Language: Английский

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Mini-encyclopedia of mitochondria-relevant nutraceuticals protecting health in primary and secondary care—clinically relevant 3PM innovation

The EPMA Journal, Journal Year: 2024, Volume and Issue: 15(2), P. 163 - 205

Published: April 18, 2024

Despite their subordination in humans, to a great extent, mitochondria maintain independent status but tightly cooperate with the "host" on protecting joint life quality and minimizing health risks. Under oxidative stress conditions, healthy promptly increase mitophagy level remove damaged "fellows" rejuvenating mitochondrial population sending fragments of mtDNA as SOS signals all systems human body. As long metabolic pathways are under systemic control well-concerted together, adaptive mechanisms become triggered increasing protection, activating antioxidant defense repair machinery. Contextually, attributes patho-/physiology instrumental for predictive medical approach cost-effective treatments tailored individualized patient profiles primary (to protect vulnerable individuals again health-to-disease transition) secondary affected disease progression) care. Nutraceuticals naturally occurring bioactive compounds demonstrating health-promoting, illness-preventing, other health-related benefits. Keeping mind health-promoting properties nutraceuticals along therapeutic potential safety profile, there is permanently growing demand application mitochondria-relevant nutraceuticals. Application beneficial only if meeting needs at individual level. Therefore, risk assessment creation pivotal importance followed by adapted nutraceutical sets needs. Based scientific evidence available nutraceuticals, this article presents examples frequent which require protective measures targeted holistic following advanced concepts predictive, preventive, personalized medicine (PPPM/3PM)

Language: Английский

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The potential influence of melatonin on mitochondrial quality control: a review

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 11, 2024

Mitochondria are critical for cellular energetic metabolism, intracellular signaling orchestration and programmed death regulation. Therefore, mitochondrial dysfunction is associated with various pathogeneses. The maintenance of homeostasis functional recovery after injury coordinated by biogenesis, dynamics autophagy, which collectively referred to as quality control. There increasing evidence that mitochondria important targets melatonin exert protective effects under pathological conditions. Melatonin, an evolutionarily conserved tryptophan metabolite, can be synthesized, transported metabolized in mitochondria. In this review, we summarize the role damaged elimination energy supply regulating control, may provide new strategies clinical treatment mitochondria-related diseases.

Language: Английский

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Melatonin ameliorates 10‐hydroxycamptothecin‐induced oxidative stress and apoptosis via autophagy‐regulated p62/Keap1/Nrf2 pathway in mouse testicular cells

Journal of Pineal Research, Journal Year: 2024, Volume and Issue: 76(4)

Published: May 1, 2024

Abstract 10‐Hydroxycamptothecin (HCPT) is a widely used clinical anticancer drug but has significant side effect profile. Melatonin beneficial impact on the chemotherapy of different cancer cells and reproductive processes, underlying molecular mechanism melatonin's involvement in HCPT‐induced effects cells, especially testicular are poorly understood. In this study, we found that melatonin therapy significantly restored cell damage did not affect antitumor HCPT. Further analysis suppressed DNA associated with ataxia‐telangiectasia mutated‐ Rad3‐related CHK1 phosphorylation levels testis. Changes apoptosis‐associated protein (Bax, Bcl‐2, p53, Cleaved caspase‐3) reactive oxygen species‐associated proteins (Nrf2 Keap1) index (malondialdehyde glutathione) suggested treatment relieved apoptosis oxidative damage, respectively. Mechanistically, melatonin‐activated autophagy (ATG7, Beclin1, LC3bII/I) may induce p62‐dependent to degrade Keap1, eliciting Nrf2 from Keap1‐Nrf2 interaction promote antioxidant enzyme expression such as HO‐1, which would salvage ROS production mitochondrial dysfunction. Collectively, study reveals protect via activation autophagy, alleviates stress, dysfunction, apoptosis.

Language: Английский

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Therapeutic contribution of melatonin to the treatment of septic cardiomyopathy: A novel mechanism linking Ripk3-modified mitochondrial performance and endoplasmic reticulum function

Redox Biology, Journal Year: 2019, Volume and Issue: 26, P. 101287 - 101287

Published: July 27, 2019

The basic pathophysiological mechanisms underlying septic cardiomyopathy have not yet been completely clarified. Disease-specific treatments are lacking, and care is still based on supportive modalities. aim of our study was to assess the protective effects melatonin cardiomyopathy, with a focus interactions between receptor-interacting protein kinase 3 (Ripk3), mitochondria, endoplasmic reticulum (ER) cytoskeletal degradation in cardiomyocytes. Ripk3 expression increased heart samples challenged LPS, followed by myocardial inflammation, cardiac dysfunction, breakdown cardiomyocyte death. treatment attenuated injury comparable manner genetic depletion Ripk3. Molecular investigations revealed that intimately regulated mitochondrial function, ER stress, homeostasis cardioprotective signaling pathways. Melatonin-mediated inhibition improved bioenergetics, reduced mitochondria-initiated oxidative damage, sustained dynamics, ameliorated normalized calcium recycling, activated pathways (including AKT, ERK AMPK) Interestingly, overexpression mediated resistance therapy following infection LPS-treated hearts an adenovirus expressing Altogether, findings identify upregulation as novel risk factor for development sepsis-related injury, restores physiological functions ER, contractile cytoskeleton Additionally, data also reveal new, potentially therapeutic mechanism which protects from sepsis-mediated possibly targeting

Language: Английский

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