Immacolata Castellano

University of Naples Federico II | UNINA · Department of Molecular Medicine and Medical Biotechnology

One of the major threats to skin aging and the risk of developing skin cancer is excessive exposure to the sun’s ultraviolet radiation (UVR). The use of sunscreens containing different synthetic, organic, and inorganic UVR filters is one of the most widespread defensive measures. However, increasing evidence suggests that some of these compounds ar...

Diatoms represent one of the most abundant groups of microalgae in the ocean and are responsible for approximately 20% of photosynthetically fixed CO2 on Earth. Due to their complex evolutionary history and ability to adapt to different environments, diatoms are endowed with striking molecular biodiversity and unique metabolic activities. Their hig...

Among natural products, ovothiol (ovo), produced by marine invertebrates, bacteria, and microalgae, is receiving increasing interest for its unique antioxidant properties. Recently, ovo has been shown to exhibit anti-inflammatory activity in an in vitro model of endothelial dysfunction and in an in vivo model of liver fibrosis. The aim of this stud...

Ocean acidification is impacting marine life all over the world. Understanding how species can cope with the changes in seawater carbonate chemistry represents a challenging issue. We addressed this topic using underwater CO2 vents that naturally acidify some marine areas off the island of Ischia. In the most acidified area of the vents, having a m...

Ovothiols are histidine-derived thiols produced by a variety of marine invertebrates, protists and bacteria. These compounds, which are among the strongest natural antioxidants, are involved in controlling the cellular redox balance due to their redox exchange with glutathione. Although ovothiols were initially reported as protective agents against...

Nitric oxide (NO) is a pivotal signaling molecule involved in a wide range of physiological and pathological processes. We investigated NOS/NO localization patterns during the different stages of larval development in the ascidia Ciona robusta and evidenced a specific and temporally controlled pattern. NOS/NO expression starts in the most anterior...

Ovothiols are π-methyl-5-thiohistidines produced in great amounts in sea urchin eggs, where they can act as protective agents against the oxidative burst at fertilization and environmental stressors during development. Here we examined the biological relevance of ovothiol during the embryo- genesis of the sea urchin Paracentrotus lividus by assessi...

Ovothiols are sulphur-containing amino acids synthesized by marine invertebrates, protozoans, and bacteria. They act as pleiotropic molecules in signalling and protection against oxidative stress. The discovery of ovothiol biosynthetic enzymes, sulfoxide synthase OvoA and β-lyase OvoB, paves the way for a systematic investigation of ovothiol distri...

In the last few decades, the thinning of the ozone layer due to increased atmospheric pollution has exacerbated the negative effects of excessive exposure to solar ultraviolet radiation (UVR), and skin cancer has become a major public health concern. In order to prevent skin damage, public health advice mainly focuses on the use of sunscreens, alon...

Diatoms are one of the most widespread groups of microalgae on Earth. They possess extraordinary metabolic capabilities, including a great ability to adapt to different light conditions. Recently, we have discovered that the diatom Skeletonema marinoi produces the natural antioxidant ovothiol B, until then identified only in clams. In this study, w...

Ovothiols are histidine-derived thiols that are receiving a great interest for their biological activities in human model systems. Thanks to the position of the thiol group on the imidazole ring of histidine, these compounds exhibit unusual antioxidant properties. They have been revealing a very promising pharmacological potential due to their anti...

Marine pollution due to disused industrial activities is a major threat to ecosystems and human health, for example through the effects of re-suspension of toxic substances that are present in contaminated sediments. Here, we examined the effects of different re-suspension patterns of polluted sediments from the site of national interest Bagnoli-Co...

Plastic pollution represents one of the major threats to the marine environment. A wide range of marine organisms has been shown to ingest microplastics due to their small dimensions (less than 1 mm). This negatively affects some biological processes, such as feeding, energy reserves and reproduction. Very few studies have been performed on the eff...

Sulfoxide synthases are enzymes involved in the biosynthesis of small sulfur-containing natural products. Their enzymatic activity represents a unique sulfur transfer strategy in nature that is the insertion of a sulfur atom on the imidazole ring of histidine. To date, only two enzymes are known to carry out this function: the sulfoxide synthase Eg...

Gamma-glutamyl transpeptidase (GGT) is a cell surface enzyme involved in glutathione metabolism and maintenance of redox homeostasis. High expression of GGT on tumor cells is associated with an increase of cell proliferation and resistance against chemotherapy. GGT inhibitors that have been evaluated in clinical trials are too toxic for human use....

Liver fibrosis is a pathophysiologic process involving the accumulation of extracellular matrix proteins as collagen deposition. Advanced liver fibrosis can evolve in cirrhosis, portal hypertension and often requires liver transplantation. At the cellular level, hepatic fibrosis involves the activation of hepatic stellate cells and their transdiffe...

Decommissioned industrial activities cause an accumulation of different xenobiotic inquinants, especially into the water bodies, with a tremendous impact on ecosystem functioning and human health. The Site of National Interest (SIN) Bagnoli-Coroglio, a post-industrial iron and steel activity site, represents a paradigmatic case study in the South o...

Gamma-glutamyl transpeptidase (GGT) is an enzyme located on the surface of cellular membranes and involved in glutathione metabolism and maintenance of redox homeostasis. High GGT expression on tumor cells is associated with increased cell proliferation and resistance against chemotherapy. GGT inhibitors evaluated so far in clinical trials are too...

Marine environment is a great source of bioactive molecules, whose biological properties and applications are often used especially to prevent skin diseases and aging caused by UVAexposure.Ovothiols are methyl5thiohistidines from marine invertebrates, bacteria, and microalgae, which protect cells from environmental stressors. Recently, we have show...

The most abundant marine sulfur-containing compounds are probably ovothiols, histidine-derived thiols, isolated from marine invertebrates, microalgae, and proteobacteria. In sea urchin eggs ovothiols play a key role in the protection of cells towards the oxidative burst associated with fertilization by controlling the cellular redox balance and rec...

Ovothiol is a marine p-methyl-5-thiohistidine showing peculiar antioxidant properties, due to the position of the thiol group (-SH) on the imidazole ring. It is produced in large amounts in sea urchin eggs to protect them from the oxidative burst at fertilisation and developing embryos from environmental cues. In this work, the temporal and spatial...

5-thiohistidines are histidine-derived thiols first isolated from marine invertebrates eggs where they play a key role in the protection of cells towards the oxidative burst associated with fertilization. Ovothiols are methyl-5-thiohistidines from marine invertebrates, bacteria, and microalgae, which protect cells from environmental stressors. Rece...

Liver fibrosis is a complex process caused by chronic hepatic injury, which leads to an excessive increase in extracellular matrix protein accumulation and fibrogenesis. Several natural products, including sulfur-containing compounds, have been investigated for their antifibrotic effects; however, the molecular mechanisms underpinning their action...

Ovothiol is a marine π-methyl-5-thiohistidine produced in large amounts by sea urchin eggs to protect them from oxidative burst at fertilisation and developing embryos from environmental cues. The key enzyme responsible for ovothiol biosynthesis, a 5-histidylcysteine sulfoxide synthase (OvoA), has been found in several genomes, including diatoms. D...

Ovothiols are histidine‐derived thiols found in many marine invertebrates (Paracentrotus lividus, Strongylocentrotus purpuratus, Arbacia lixula, Marthasterias glacialis, Astropecten aurantiacus, Octopus vulgaris, Loligo vulgaris, and Platynereis dumerilii), as well as in algae and protozoa. Different aspects related to ovothiols are examined in thi...

Covering: up to 2018 Ovothiols are sulfur-containing natural products biosynthesized by marine invertebrates, microalgae, and bacteria. These compounds are characterized by unique chemical properties suggestive of numerous cellular functions. For example, ovothiols may be cytoprotectants against oxidative stress, serve as building blocks of more co...

Most of the studies regarding the impact of ocean acidification on macroalgae have been carried out for short-term periods, in controlled laboratory conditions, thus hampering the possibility to scale up the effects on long-term. In the present study, the volcanic CO2 vents off Ischia Island were used as a natural laboratory to investigate the meta...

Chronic hyperglycemia is associated with oxidative stress and vascular inflammation, both leading to endothelial dysfunction and cardiovascular disease that can be weakened by antioxidant/anti-inflammatory molecules in both healthy and diabetic subjects. Among natural molecules, ovothiol A, produced in sea urchin eggs to protect eggs/embryos from t...

The major yolk protein toposome plays crucial roles during gametogenesis and development of sea urchins. We previously found that nitration of toposome increases in the gonads of a Paracentrotus lividus population living in a marine protected area affected by toxic blooms of Ostreospsis cf. ovata, compared to control populations. This modification...

Marine thiohistidines are sulphur-containing compounds, which play a key role in maintaining cellular redox homeostasis and in the survival of organisms constantly exposed to environmental constraints. Among them, methyl-5-thiohistidines (ovothiols) are isolated in large amounts in sea urchin eggs, and display unique antioxidant properties, thanks...

EMBRIC Transnational Access Programme Project title "Discovery of cosmeceutical and pharmaceutical properties of a promising marine natural product "

The extraordinary beauty and the richness in biodiversity of marine landscapes reflect millions of years of evolution and adaptation of life to changing environments. Sulphur-containing compounds play a key role in maintaining cellular redox homeostasis and in the survival of organisms constantly exposed to environmental constraints. Among them, 5-...

Studies regarding macroalgal responses to ocean acidification (OA) are mostly limited to short-term experiments in controlled conditions, which hamper the possibility to scale up the observations to long-term effects in the natural environment. To gain a broader perspective, we utilized volcanic CO2 vents as a “natural laboratory” to study OA effec...

Background: Heavy rare earth elements (HREEs) have been scarcely studied for their toxicity, in spite of their applications in several technologies. Thus HREEs require timely investigations for their adverse health effects. Methods: Paracentrotus lividus and Arbacia lixula embryos and sperm were exposed to trichloride salts of five HREEs (Dy, Ho...

Ocean acidification is an emerging problem that is expected to impact ocean species to varying degrees. Currently, little is known about its effect on molecular mechanisms induced in fleshy macroalgae. To elucidate genome wide responses to acidification, a comparative transcriptome analysis was carried out between Sargassum vulgare populations grow...

The health of the sea urchin Paracentrotus lividus, a key species in the Mediterranean Sea, is menaced by several pressures in coastal environments. Here, we aimed at assessing the reproductive ability of apparently healthy P. lividus population in a marine protected area affected by toxic blooms of Ostreopsis cf. ovata. Wide-ranging analyses were...

Ovothiol, isolated from marine invertebrate eggs, is considered one of the most powerful antioxidant with potential for drug development. However, its biological functions in marine organisms still represent a matter of debate. In sea urchins, the most accepted view is that ovothiol protects the eggs by the high oxidative burst at fertilization. In...

Metal contamination represents one of the major sources of pollution in marine environments. In this study we investigated the short-term effects of ecologically relevant cadmium and manganese concentrations (10(-6) and 3.6 x 10(-5) M, respectively) on females of the sea urchin Paracentrotus lividus and their progeny, reared in the absence or prese...

Nitric oxide is a versatile and powerful signaling molecule in plants. However, most of our understanding stems from studies on terrestrial plants and very little is known about marine autotrophs. This review summarizes current knowledge about the source of nitric oxide synthesis in marine photosynthetic organisms and its role in various physiologi...

Polyunsaturated aldehydes (PUAs) are fatty-acid-derived metabolites produced by some microalgae, including different diatom species. PUAs are mainly produced as a wound-activated defence mechanism against microalgal predators or released from senescent cells at the end of a bloom. PUAs, including 2,4-trans-decadienal (DD), induce deleterious effect...

In invertebrates, the physiological messenger nitric oxide (NO), produced by L-arginine oxidation by NO synthase (NOS), is involved in a variety of processes, including development, feeding, defense, bioluminescence, neural transmission, immune response, swimming. In sea urchins, NO is implicated in important processes occurring at fertilization an...

In the ascidian Ciona intestinalis larval development and metamorphosis require a complex interplay of events, including nitric oxide (NO) production, MAP kinases (ERK, JNK) and caspase-3 activation. We have previously shown that NO levels affect the rate of metamorphosis, regulate caspase activity and promote an oxidative stress pathway, resulting...

Ovothiols are histidine-derived thiols isolated from sea urchin eggs, where they play a key role in the protection of cells toward the oxidative burst associated with fertilization by controlling the cellular redox balance and recycling oxidized glutathione. In this study, we show that treatment of a human liver carcinoma cell line, Hep-G2, with ov...

The sea urchin Paracentrotus lividus, a keystone herbivore in the Mediterranean Sea, is a good model system to study the response to environmental stress. Recently, it has been shown that the physiological messenger nitric oxide (NO), produced by L-arginine oxidation by NO synthase (NOS), is involved in the stress response induced by the diatom ald...

Gamma-glutamyl transpeptidases (c-GTs) belong to the N-terminal nucleophile hydrolase superfamily, enzymes that cleave the c-glutamyl amide bond of glutathione to give cysteinylglycine. The released c-glutamyl group can be transferred to water (hydrolysis) or to amino acids or short peptides (transpeptidation). c-GT plays a key role in the gamma-gl...

In invertebrates, the pluripotent gas, nitric oxide (NO) is involved in a variety of processes including development, feeding, defence, bioluminescence, neural transmission, immune response, swimming. In sea urchin, NO is implicated in important processes occurring at fertilization and at later developmental stages, where it acts as a signalling mo...

The transpeptidation activity of γ-glutamyltranspeptidase from Geobacillus thermodenitrificans (GthGT) is negligible and the enzyme is highly thermostable. Here we have examined the effect of concentrated NaCl solutions on structure, stability, dynamics and enzymatic activity of GthGT. The protein exhibited hydrolytic activity over a broad range of...

γ-Glutamyltranspeptidases (γ-GTs) are ubiquitous enzymes that catalyze the hydrolysis of γ-glutamyl bonds in glutathione and glutamine and the transfer of the released γ-glutamyl group to amino acids or short peptides. These enzymes are involved in glutathione metabolism and play critical roles in antioxidant defense, detoxification, and inflammati...

c-Glutamyltranspeptidase (c-GT) is an ubiqui-tous enzyme that catalyzes the hydrolysis of c-glutamyl bonds in glutathione and glutamine and the transfer of the released c-glutamyl group to amino acids or short peptides. c-GTs from extremophiles, bacteria adapted to live in hostile environments, were selected as model systems to study the molecular...

g-Glutamyltranspeptidase (g-GT) is an ubiqui-tous enzyme that catalyzes the hydrolysis of g-glutamyl bonds in glutathione and glutamine and the transfer of the released c-glutamyl group to amino acids or short peptides. g-GTs from extremophiles, bacteria adapted to live in hostile environments, were selected as model systems to study the molecular...

γ-Glutamyltranspeptidase (γ-GT) is an ubiquitous enzyme that catalyzes the hydrolysis of γ-glutamyl bonds in glutathione and glutamine and the transfer of the released γ-glutamyl group to amino acids or short peptides. γ-GTs from extremophiles, bacteria adapted to live in hostile environments, were selected as model systems to study the molecular u...

Superoxide dismutases (SODs) are metalloenzymes catalysing the dismutation of superoxide anion radicals into molecular oxygen and hydrogen peroxide. Here, we present the crystal structure of a cold-adapted Fe-SOD from the Antarctic eubacterium Pseudoalteromonas haloplanktis (PhSOD), and that of its complex with sodium azide. The structures were com...

Streptococcus mutans, the main pathogen involved in the development of dental caries, is an aerotolerant microorganism. The bacterium lacks cytochromes and catalase, but possesses other antioxidant enzymes, such as superoxide dismutase (SmSOD). Previous researches suggested that SmSOD belongs to the 'cambialistic' group, functioning with Fe or Mn i...

Nerve growth factor (NGF) induces terminal differentiation in PC12, a pheochromocytoma-derived cell line. NGF binds a specific receptor on the membrane and triggers the ERK1/2 cascade, which stimulates the transcription of neural genes. We report that NGF significantly affects mitochondrial metabolism by reducing mitochondrial-produced reactive oxy...

Gamma-glutamyltranspeptidases (γ-GTs) catalyze the transfer of the gamma-glutamyl moiety of glutathione and related gamma-glutamyl amides to water (hydrolysis) or to amino acids and peptides (transpeptidation) and play a key role in glutathione metabolism. Recently, γ-GTs have been considered attractive pharmaceutical targets for cancer and useful...

Diclofenac, a nonsteroidal anti-inflammatory drug, induces apoptosis on the neuroblastoma cell line SH-SY5Y through a mitochondrial dysfunction, affecting some antioxidant mechanisms. Indeed, the time- and dose-dependent increase of apoptosis is associated to an early enhancement of the reactive oxygen species (ROS). Mitochondrial superoxide dismut...

The role of three amino acid residues (Q143, Y34, S82) of rat mitochondrial superoxide dismutase (ratSOD2) in the enzymatic activity, thermostability, and post-translational modification of the enzyme was investigated through site-directed mutagenesis studies. Six recombinant forms of the enzyme were produced, carrying the Q143 or H143 residue with...

Chlorophyll (Chl) is a tetrapyrrole macrocycle containing Mg and a phytol chain. The Chl biosynthetic pathway consists of the multi-enzymatic reactions. An asymmetric conjugated double bond system of Chl a, which is crucial for efficient light absorption, is formed in the penultimate step of biosynthesis, reducing protochlorophyllide (Pchlide) to f...

Our previous work showed that the adduct between beta-mercaptoethanol and the single cysteine residue (Cys57) in superoxide dismutase from the psychrophilic eubacterium Pseudoalteromonas haloplanktis (PhSOD) reduces the enzyme inactivation by peroxynitrite. In this work, immunoblotting experiments prove that peroxynitrite inactivation of PhSOD invo...

The Antarctic eubacterium Pseudoalteromonas haloplanktis (Ph) produces a cold-active iron superoxide dismutase (SOD). PhSOD is a homodimeric enzyme, that displays a high catalytic activity even at low temperature. Using hanging-drop vapour-diffusion technique, PhSOD has been successfully crystallized in two different crystal forms. Both crystal for...

The growth temperature adaptation of six model proteins has been studied in 42 microorganisms belonging to eubacterial and archaeal kingdoms, covering optimum growth temperatures from 7 to 103 degrees C. The selected proteins include three elongation factors involved in translation, the enzymes glyceraldehyde-3-phosphate dehydrogenase and superoxid...

This work reports properties of typical enzyme redox systems in Pseudoalteromonas haloplanktis (Ph), a psychrophilic eubacterium isolated from marine Antarctic sediments. The enzymes investigated are superoxide dismutase (PhSOD) and the components of the thioredoxin system, namely thioredoxin (PhTrx) and thioredoxin reductase (PhTrxR), altogether i...

A psychrophilic superoxide dismutase (SOD) has been characterized from the Antarctic eubacterium Pseudoalteromonas haloplanktis (Ph). PhSOD is a homodimeric iron-containing enzyme and displays a high specific activity, even at low temperature. The enzyme is inhibited by sodium azide and inactivated by hydrogen peroxide; it is also very sensitive to...

The ubiquitous and pleiotropic dual specificity protein kinase CK2 has been studied and characterized in many organisms, from yeast to mammals. Generally, the enzyme is composed of two catalytic (alpha and/or alpha') and two regulatory (beta) subunits, forming a differently assembled tetramer. Although prone to controversial interpretation, the fun...

The ubiquitous and pleiotropic dual specificity protein kinase CK2 has been studied and characterized in many organisms, from yeast to mammals. Generally, the enzyme is composed of two catalytic (α and/or α′) and two regulatory (β) subunits, forming a differently assembled tetramer. Although prone to controversial interpretation, the function of CK...