Protection of glucotoxicity by a tripeptide derivative of α‐melanocyte‐stimulating hormone in human epidermal keratinocytes

Gkogkolou, Paraskevi; Sarna, Michał; Sarna, Tadeusz; Paus, Ralf; Luger, Thomas A.; Böhm, Markus

doi:10.1111/bjd.17125

Cited by 12 publications

(9 citation statements)

References 53 publications

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“…In melanocytes and in melanoma cells, melanin synthesis is controlled by a cascade of enzymatic reactions beginning with the oxidation of tyrosine to L‐3,4‐dihydroxyphenylalanine (L‐DOPA) by tyrosinase (TYR), the rate‐limiting enzyme of melanogenesis 1,2. Among the hormonal regulators of melanin synthesis,3 α‐melanocyte‐stimulating hormone (α‐MSH),5-8 a product of POMC processing, plays an important role. It interacts with a specific cell surface melanocortin 1 receptor (MC1R) stimulating melanin synthesis and other differentiated functions of melanocytes 8,9.…”

Section: Introductionmentioning

confidence: 99%

Melatonin exerts oncostatic capacity and decreases melanogenesis in human MNT‐1 melanoma cells

Kleszczyński

Kim

Bilska

et al. 2019

Journal of Pineal Research

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Melanogenesis is a key parameter of differentiation in melanocytes and melanoma cells; therefore, search for factors regulating this pathway are strongly desired.Herein, we investigated the effects of melatonin, a ubiquitous physiological mediator that is found throughout animals and plants. In mammals, the pineal gland secretes this indoleamine into the blood circulation to exert an extensive repertoire of biological activities. Our in vitro assessment indicates an oncostatic capacity of melatonin in time-dependent manner (24, 48, 72 hours) in highly pigmented MNT-1 melanoma cells. The similar pattern of regulation regarding cell viability was observed in amelanotic Sk-Mel-28 cells. Subsequently, MNT-1 cells were tested for the first time for evaluation of melanin/melatonin interaction. Thus primary, electron paramagnetic resonance (EPR) spectroscopy demonstrated that melatonin reduced melanin content. Artificially induced disturbances of melanogenesis by selected inhibitors (N-phenylthiourea or kojic acid) were slightly antagonized by melatonin.Additionally, analysis using transmission electron microscopy has shown that melatonin, particularly at higher dose of 10 −3 mol/L, triggered the appearance of premelanosomes (stage I-II of melanosome) and MNT-1 cells synthesize de novo endogenous melatonin shown by LC-MS. In conclusion, these studies show a melanogenic-like function of melatonin suggesting it as an advantageous agent for treatment of pigmentary disorders. K E Y W O R D Selectron paramagnetic resonance spectroscopy, liquid chromatography-mass spectroscopy, melanogenesis, melanoma cells, melatonin, transmission electron microscopy, tyrosinase activity

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Section: Introductionmentioning

confidence: 99%

Melatonin exerts oncostatic capacity and decreases melanogenesis in human MNT‐1 melanoma cells

Kleszczyński

Kim

Bilska

et al. 2019

Journal of Pineal Research

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“…The α‐MSH analog afamelanotide showed promising results as a treatment for solar urticaria, [ 43 ] vitiligo, [ 46,47 ] acne vulgaris [ 49 ] and KdPT is a promising candidate for the treatment of ulcerative colitis, [ 53 ] psoriasis [ 54 ] and diabetic wound healing. [ 55 ] Some drug candidates are novel substances, while others have already been approved for diverse indications, which may or may not include skin diseases) and are now being repurposed for specific indications. This “drug repositioning” is a complex process, but has advantages, in particular for indications where drug development is less profitable.…”

Section: Discussionmentioning

confidence: 99%

“…Other interesting effects of KdPT are attenuation of high glucose‐induced oxidative stress and antagonization of the effects of glucose on cell viability, metabolic activity and migration in a skin organ culture model. [ 55 ] These effects make KdPT a promising drug candidate for preclinical studies on diabetic wound healing. [ 55 ] Moreover, under proinflammatory conditions KdPT had immunomodulatory effects on human scalp hair follicles [ 56 ] ex vivo and stimulated hair follicle pigmentation in situ.…”

Section: Pro‐opiomelanocortin (Pomc) and Pomc‐derived Peptidesmentioning

confidence: 99%

“…[ 55 ] These effects make KdPT a promising drug candidate for preclinical studies on diabetic wound healing. [ 55 ] Moreover, under proinflammatory conditions KdPT had immunomodulatory effects on human scalp hair follicles [ 56 ] ex vivo and stimulated hair follicle pigmentation in situ. [ 57 ] The clinical development in ulcerative colitis is ongoing.…”

Section: Pro‐opiomelanocortin (Pomc) and Pomc‐derived Peptidesmentioning

confidence: 99%

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Current and emerging treatments targeting the neuroendocrine system for disorders of the skin and its appendages

Soeberdt

Kilić

Abels

2020

Experimental Dermatology

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The skin as a neuroendocrine organ and the role of neuroendocrine signalling in the development of disorders affecting the skin and its appendages has received increasing attention in the last years. Different neuroendocrine systems have been described in the barrier organ skin, including the thyroid system, the hypothalamicpituitary-adrenal axis, the opioid, the endocannabinoid, the cholinergic, the secosteroidogenic and the serotonergic systems. All of these systems have been implicated in the development of skin diseases, which often have an inflammatory origin. These discoveries have led to an increase in the development of new drugs targeting components of neuroendocrine signalling pathways. Additionally, attempts have been made to repurpose already approved drugs targeting neuroendocrine signalling pathways in other organs for the treatment of skin diseases. Recently published results from preclinical and clinical studies look promising and may offer improved therapies to patients suffering from skin diseases in the near future. In this review, from a pharmaceutical point of view, we focus on recent progress in synthetic drug development of compounds targeting neuroendocrine signalling in the skin and its appendages to treat skin diseases such as atopic dermatitis, psoriasis, acne, alopecia areata and hyperhidrosis.

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“…The number of elderly individuals in large developing countries such as India and China also will increase from five percent to ten percent over the next several decades (3, 4). For developed nations, the development of new and effective strategies for multiple disorders that include cardiovascular disease (5-9), glucose regulation (10)(11)(12)(13)(14)(15), and metabolic disease (15)(16)(17)(18)(19) as well as access to preventive care measures have contributed to the increased life span of the world's population.…”

Section: The Global Aging Of the World's Populationmentioning

confidence: 99%

Sirtuins: Developing Innovative Treatments for Aged-Related Memory Loss and Alzheimer’s Disease

Maiese¹

2019

CNR

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The world's population continues to age at a rapid pace. By the year 2050, individuals over the age of 65 will account for sixteen percent of the world's population and life expectancy will increase well over eighty years of age. Accompanied with the aging of the global population is a significant rise in non-communicable diseases (NCDs). Neurodegenerative disorders will form a significant component for NCDs. Currently, dementia is the 7 th leading cause of death and can be the result of multiple causes that include diabetes mellitus, vascular disease, and Alzheimer's disease (AD). AD may represent at least sixty percent of these cases. Current treatment for these disorders is extremely limited to provide only some symptomatic relief at present. Sirtuins and in particular, the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), represent innovative strategies for the treatment of cognitive loss. New work has revealed that SIRT1 provides protection against memory loss through mechanisms that involve oxidative stress, Aβ toxicity, neurofibrillary degeneration, vascular injury, mitochondrial dysfunction, and neuronal loss. In addition, SIRT1 relies upon other avenues that can include trophic factors, such as erythropoietin, and signaling pathways, such as Wnt1 inducible signaling pathway protein 1 (WISP1/CCN4). Yet, SIRT1 can have detrimental effects as well that involve tumorigenesis and blockade of stem cell differentiation and maturation that can limit reparative processes for cognitive loss. Further investigations with sirtuins and SIRT1 should be able to capitalize upon these novel targets for dementia and cognitive loss.

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Protection of glucotoxicity by a tripeptide derivative of α‐melanocyte‐stimulating hormone in human epidermal keratinocytes

Abstract: Our findings highlight a novel effect of KdPT that could be exploited for the future therapy of diabetic skin ulcers.

Cited by 12 publications

References 53 publications

Melatonin exerts oncostatic capacity and decreases melanogenesis in human MNT‐1 melanoma cells

Melatonin exerts oncostatic capacity and decreases melanogenesis in human MNT‐1 melanoma cells

Current and emerging treatments targeting the neuroendocrine system for disorders of the skin and its appendages

Sirtuins: Developing Innovative Treatments for Aged-Related Memory Loss and Alzheimer’s Disease

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