González‐Santoyo, I. & Córdoba‐Aguilar, A. Phenoloxidase: a key component of the insect immune system. Entomol. Exp. Appl. 142, 1–16 (2012). a b Mosse, Irma B.; Dubovic, Boris V.; Plotnikova, Svetlana I.; Kostrova, Ludmila N.; Molophei, Vadim; Subbot, Svetlana T.; Maksimenya, Inna P. (20–25 May 2001). Obelic, B.; Ranogajev-Komor, M.; Miljanic, S.; Krajcar Bronic, I. (eds.). Melanin is Effective Radioprotector against Chronic Irradiation and Low Radiation Doses. IRPA Regional Congress on Radiation Protection in Central Europe: Radiation Protection and Health. INIS. Dubrovnik (Croatia): Croatian Radiation Protection Association. p.35 (of 268).

The melanin in the skin is produced by melanocytes, which are found in the basal layer of the epidermis. Although, in general, human beings possess a similar concentration of melanocytes in their skin, the melanocytes in some individuals and ethnic groups produce variable amounts of melanin. Some humans have very little or no melanin synthesis in their bodies, a condition known as albinism. [6]Early humans evolved to have dark skin color around 1.2million years ago, as an adaptation to a loss of body hair that increased the effects of UV radiation. Before the development of hairlessness, early humans had reasonably light skin underneath their fur, similar to that found in other primates. [63] The most recent scientific evidence indicates that anatomically modern humans evolved in Africa between 200,000 and 100,000 years ago, [64] and then populated the rest of the world through one migration between 80,000 and 50,000 years ago, in some areas interbreeding with certain archaic human species ( Neanderthals, Denisovans, and possibly others). [65] It seems likely that the first modern humans had relatively large numbers of eumelanin-producing melanocytes, producing darker skin similar to the indigenous people of Africa today. As some of these original people migrated and settled in areas of Asia and Europe, the selective pressure for eumelanin production decreased in climates where radiation from the sun was less intense. This eventually produced the current range of human skin color. Of the two common gene variants known to be associated with pale human skin, Mc1r does not appear to have undergone positive selection, [66] while SLC24A5 has undergone positive selection. [67] Effects [ edit ]

Protection against reactive oxygen species (ROS). Reactive oxygen species are byproducts of your body’s cell processes. When ROS accumulate in your cells, they can lead to stress, premature aging and health concerns such as diabetes and cancer. Melanin scavenges for ROS, boosting antioxidants and eliminating free radicals.Mylonakis, E. et al. Galleria mellonella as a model system to study Cryptococcus neoformans pathogenesis. Infect. Immun. 73, 3842–3850 (2005). Micrograph of Melanin pigment (light refracting granular material—center of image) in a pigmented melanoma. Micrograph of the epidermis, with melanin labeled at left. During cryptococcal infection of G. mellonella, melanin encapsulation of the fungus within nodules was associated with diminished or lost fluorescence signal in these GFP-expressing C. neoformans strains. Additionally, the melanin-encapsulated fungi that remained GFP-positive had weaker signals and the intensity of the GFP signal was more intense for the non-melanin-encapsulated fungi within the nodules. The expression of GFP in these cells is under the control of an actin promotor, and while actin is generally presumed to be constitutively expressed in cells, growth conditions have been shown to lead to some alterations in cryptococcal actin expression 49, 50. If the environmental conditions within the nodule abolished actin expression in some cells without killing the fungus, we would expect that condition to equally affect the melanin and non-melanin-encapsulated fungi, and as a result, see similar GFP-negative: GFP-positive ratios between the melanin-encapsulated and not melanin-encapsulated cells. The association between melanin encapsulation and disappearance in GFP fluorescence provides strong evidence for the notion that the melanization reaction kills fungal cells during infection. This is the first evidence, to the best of our understanding, that G. mellonella immune melanization directly and effectively neutralizes C. neoformans during infection and demonstrated that melanin encapsulation results in fungal death within the insect. Previously, the death of microbes, specifically bacteria, was attributed to the enzymatic activity of the melanin-producing phenoloxidase (PO) in an in vitro reaction 16. In addition to our association of melanin encapsulation and fungal death in vivo, we sought to reproduce these results in vitro using extracted hemolymph in buffer. We used the PO-specific inhibitor, phenylthiourea (PTU), we found that PO-inhibited wells of hemolymph had higher recoverable CFUs of C. neoformans compared to the uninhibited wells. The inverse correlation of melanization with CFUs further supports the claim that melanin plays a role in neutralizing C. neoformans. Since we only assayed CFUs from these in vitro experiments, we cannot determine whether the melanization in the in vitro experiments directly killed the fungus or just inhibited fungal growth.

We used these techniques to compare the immune melanization between C. neoformans and C. albicans, the latter of which is known to trigger robust melanization of the hemolymph 39. Following infection, C. albicans activated the melanization response faster (beginning as early as 15 min) and to a significantly greater extent than did C. neoformans (Fig. 2h). These data showing large amounts of melanization induced by C. albicans corresponds to the levels of melanization previously reported that occurs during G. mellonella infection with C. albicans versus C. neoformans and further validates the developed methodology 39. Evaluating the melanin-based immune response of G. mellonella using tissue clearing

Prodigiosin

Notably, we observed the formation of melanin-evasive pseudohyphae in C. auris when exposed to the G. mellonella hemolymph. These findings corroborate previous studies showing that C. auris forms pseudohyphae during G. mellonella infection 54, and indicate that the stress and cues from the hemolymph can induce morphological changes in multiple fungal species. Pseudohyphae and enlarged giant cells in C. auris have been previously linked to exposure to genotoxic stress, indicating that the melanization reaction can induce DNA damage 55. Following tissue clearing of C. auris infected larvae, we observed pseudohyphal structures in situ. We also observed melanin-encapsulated fungi within aggregates surrounding trachea, as previously reported 54, 56, although the frequency of this association was difficult to ascertain, with aggregates of melanin-encapsulated C. auris was also found unassociated with trachea, including in the insect’s head capsule. Smith, D. F. Q. & Casadevall, A. Fungal immunity and pathogenesis in mammals versus the invertebrate model organism Galleria mellonella. Pathogens Dis 79, 1–25 (2021). Meredith P, Riesz J (2004). "Radiative relaxation quantum yields for synthetic eumelanin". Photochemistry and Photobiology. 79 (2): 211–6. arXiv: cond-mat/0312277. doi: 10.1111/j.1751-1097.2004.tb00012.x. PMID 15068035. S2CID 222101966. Castelvecchi, Davide (26 May 2007). "Dark Power: Pigment seems to put radiation to good use". Science News. 171 (21): 325. doi: 10.1002/scin.2007.5591712106.

Meredith, Paul; Sarna, Tadeusz (1 December 2006). "The physical and chemical properties of eumelanin". Pigment Cell Research. 19 (6): 572–594. doi: 10.1111/j.1600-0749.2006.00345.x. PMID 17083485. Mouchet, Sébastien R; Deparis, Olivier (2021), Natural Photonics and Bioinspiration (1sted.), Artech House, ISBN 978-163-081-797-8 Fang, W., Fernandes, É. K. K., Roberts, D. W., Bidochka, M. J. & St. Leger, R. J. A laccase exclusively expressed by Metarhizium anisopliae during isotropic growth is involved in pigmentation, tolerance to abiotic stresses and virulence. Fungal Genet. Biol. 47, 602–607 (2010). Following the hemocyte washes, 1 ml of cell-free hemolymph was added to the entirety of the MatTek dish, followed by an addition 1 ml of IPS. The MatTek dish was covered and imaged using the OpenFlexure microscope and software and time-lapse microscopy was performed every minute for 16–24 h 63. Control experiments without added fungus or fungal components, or with anticoagulation buffer to inhibit melanization and coagulation, were performed (Supplementary Movies 11 and 12). This protocol is summarized in Supplementary Fig. 3b. Recent research suggests that melanin may serve a protective role other than photoprotection. [69] Melanin is able to effectively chelate metal ions through its carboxylate and phenolic hydroxyl groups, in many cases much more efficiently than the powerful chelating ligand ethylenediaminetetraacetate (EDTA). Thus, it may serve to sequester potentially toxic metal ions, protecting the rest of the cell. This hypothesis is supported by the fact that the loss of neuromelanin observed in Parkinson's disease is accompanied by an increase in iron levels in the brain.a b Sarna, Michal; Krzykawska-Serda, Martyna; Jakubowska, Monika; Zadlo, Andrzej; Urbanska, Krystyna (26 June 2019). "Melanin presence inhibits melanoma cell spread in mice in a unique mechanical fashion". Scientific Reports. 9 (1): 9280. Bibcode: 2019NatSR...9.9280S. doi: 10.1038/s41598-019-45643-9. ISSN 2045-2322. PMC 6594928. PMID 31243305. To further evaluate whether insect melanin promoted death of C. neoformans, fungal cells were incubated with whole extracted G. mellonella hemolymph in the presence of increasing concentrations of a phenoloxidase-specific competitive inhibitor 32, phenylthiourea (PTU). This generated a range of insect-melanin inhibiting conditions. After 24 h, a small aliquot of the hemolymph-fungal mixture was plated on nutrient rich agar to assess fungal growth. Incubation of fungus melanization-inhibited hemolymph in vitro drastically enhanced fungal growth based on CFUs, while fungal growth was nearly abolished in melanin-competent hemolymph (Fig. 1g). The number of C. neoformans CFUs following 24 h incubation in the presence of hemocytes and PTU melanin inhibitor was directly proportional to the concentration of PTU (Fig. 1g), and thus inversely proportional to the degree of melanization (Fig. 1g, inset). PTU-mediated suppression of melanization was verified by quantifying melanin intensity by mean gray value of the wells of the 96-well plate (Fig. 1g, inset). The mean gray values of the wells showed that greater suppression of melanin production by PTU treatment correlated with increasing fungal growth based on CFUs (Fig. 1h). This result strongly suggests that immune melanization inhibits the growth of C. neoformans in vitro. Control conditions with buffer and PTU alone showed that incubation with PTU did not have a negative inhibitory effect on fungal growth, nor did it account for increased fungal growth in the high concentrations. Development of a time-lapse microscopy method for studying hemocyte-fungal interactions and the melanization response Lamason RL, Mohideen MA, Mest JR, etal. (December 2005). "SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans". Science. 310 (5755): 1782–6. Bibcode: 2005Sci...310.1782L. doi: 10.1126/science.1116238. PMID 16357253. S2CID 2245002.