Disturbed melanin synthesis and chronic oxidative stress in dysplastic naevi

Pavel, S.; Nieuwpoort, Frans van; Meulen, H. van der; Out, Coby; Pizinger, Karel; Cetkovská, Petra; Smit, Nico P.M.; Koerten, Henk K.

doi:10.1016/j.ejca.2003.11.035

Cited by 75 publications

(77 citation statements)

References 40 publications

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“…In humans, melanin synthesis occurs in skin pigmentation. Excess production of melanin induces dysplastic nevi, which is a known risk factor for malignant melanoma (45). Increased melanogenesis in dysplastic nevi leads to chronic generation of ROS as byproducts and oxidative DNA damage to nevus cells (46).…”

Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalis Peptidoglycans Induce Excessive Activation of the Innate Immune System in Silkworm Larvae*

Ishii

Hamamoto

Imamura

et al. 2010

Journal of Biological Chemistry

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Porphyromonas gingivalis, a pathogen that causes inflammation in human periodontal tissue, killed silkworm (Bombyx mori, Lepidoptera) larvae when injected into the blood (hemolymph). Silkworm lethality was not rescued by antibiotic treatment, and heat-killed bacteria were also lethal. Heat-killed bacteria of mutant P. gingivalis strains lacking virulence factors also killed silkworms. Silkworms died after injection of peptidoglycans purified from P. gingivalis (pPG), and pPG toxicity was blocked by treatment with mutanolysin, a peptidoglycan-degrading enzyme. pPG induced silkworm hemolymph melanization at the same dose as that required to kill the animal. pPG injection increased caspase activity in silkworm tissues. pPGinduced silkworm death was delayed by injecting melanizationinhibiting reagents (a serine protease inhibitor and 1-phenyl-2-thiourea), antioxidants (N-acetyl-L-cysteine, glutathione, and catalase), and a caspase inhibitor (Ac-DEVD-CHO). Thus, pPG induces excessive activation of the innate immune response, which leads to the generation of reactive oxygen species and apoptotic cell death in the host tissue.The immune system is crucial for animal self-defense against pathogenic microorganisms. On the other hand, excessive activation of immune responses may cause serious damage to the host. Severely infected human patients die of septic shock and multiple organ failure, which seem to be caused by excessive activation of the host immune systems by the pathogens. The underlying pathologic mechanisms of sepsis, however, are not clear, and effective antiseptic remedies are yet to be established.In vertebrates, the immune system is divided into two categories: innate immunity and acquired immunity. Because innate immunity is the front line of host defense against pathogens and is involved in initiating acquired immune responses, it is a prominent target in studies of the pathology of diseases caused by immune system deregulation. Most of the major components of the innate immune system are conserved from vertebrates to invertebrates (1). Thus, invertebrate models with simple biologic systems are useful for studying the activation mechanisms of innate immune responses, but there are no reports of pathologic invertebrate models that are killed by excessive innate immune responses caused by bacterial invasion of the bloodstream.The silkworm, Bombyx mori, is an invertebrate model that can be administered quantitative injections of pathogens and drugs (2-4) and is suitable for the study of innate immunity (5). We recently reported that peptidoglycans and glucans, the cell wall components of bacteria and fungi, respectively, trigger the generation of reactive oxygen species (ROS) 2 from silkworm blood cells (hemocytes) followed by the activation of serine proteases and induce the activation of paralytic peptide (PP), an insect cytokine (6). At the same time, peptidoglycans and glucans induce melanization, a polymerization reaction of melanin that involves serine proteases (7,8), and phenoloxidase (a copper-conta...

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Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalis Peptidoglycans Induce Excessive Activation of the Innate Immune System in Silkworm Larvae*

Ishii

Hamamoto

Imamura

et al. 2010

Journal of Biological Chemistry

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“…Melanoma cells generate large intracellular amounts of ROS (Sander et al, 2003) and excrete them into the extra cellular space. An upgraded ROS production has also been observed in dysplastic nevi (Pavel et al, 2004). ROS emerging as bio product during physiological melanin synthesis are neutralized within melanosomes by the anti-oxidant melanin.…”

Section: Hif1/ros and Melanoma-microenvironmentmentioning

confidence: 87%

Genetic, Epigenetic and Molecular Changes in Melanoma: A New Paradigm for Biological Classification

Staibano¹,

Mascolo²,

Siano³

et al. 2011

Research on Melanoma - A Glimpse Into Current Directions and Future Trends

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“…15 Moreover, the binding of Fe 2þ to melanins initiates a further low-level oxidative stress, which together with other environmentally derived redox-active metals within melanocytes, may promote melanomagenesis.…”

Section: Discussionmentioning

confidence: 99%

Oral mucosal melanoma

Khammissa

Altini

Meer

et al. 2017

Translational Research in Oral Oncology

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Background: Oral mucosal melanoma (OMM) is relatively rare, runs an aggressive course, affects most frequently the hard palate and the maxillary gingiva, and may be multifocal. The aetiological factors and the chain of molecular events that give rise to OMM and to its growth and metastasis are largely unknown. Objectives: The purpose of this retrospective study was to characterize some clinical and histopathological features of OMM in a South African sample.

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Disturbed melanin synthesis and chronic oxidative stress in dysplastic naevi

Cited by 75 publications

References 40 publications

Porphyromonas gingivalis Peptidoglycans Induce Excessive Activation of the Innate Immune System in Silkworm Larvae*

Porphyromonas gingivalis Peptidoglycans Induce Excessive Activation of the Innate Immune System in Silkworm Larvae*

Genetic, Epigenetic and Molecular Changes in Melanoma: A New Paradigm for Biological Classification

Oral mucosal melanoma

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