On ovothiol biosynthesis and biological roles: from life in the ocean to therapeutic potential

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 complex structures and may act as molecular messengers for inter- and intracellular signaling. Detailed understanding of ovothiol physiological role in marine organisms may unearth novel concepts in cellular redox biochemistry and highlight the therapeutic potential of this antioxidant. The recent discovery of ovothiol biosynthetic genes has paved the way for a systematic investigation of ovothiol-modulated cellular processes. In this highlight we review the early research on ovothiol and we discuss key questions that may now be addressed using genome-based approaches. This highlight article provides an overview of recent progress towards elucidating the biosynthesis, function and potential application of ovothiols

From Sea to Skin: Is There a Future for Natural Photoprotectants?

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, along with wearing protective clothing and avoiding sun exposure during peak hours. Sunscreens present on the market are topical formulations that contain a number of different synthetic, organic, and inorganic UVR filters with different absorbance profiles, which, when combined, provide broad UVR spectrum protection. However, increased evidence suggests that some of these compounds cause subtle damage to marine ecosystems. One alternative may be the use of natural products that are produced in a wide range of marine species and are mainly thought to act as a defense against UVR-mediated damage. However, their potential for human photoprotection is largely under-investigated. In this review, attention has been placed on the molecular strategies adopted by marine organisms to counteract UVR-induced negative effects and we provide a broad portrayal of the recent literature concerning marine-derived natural products having potential as natural sunscreens/photoprotectants for human skin. Their chemical structure, UVR absorption properties, and their pleiotropic role as bioactive molecules are discussed. Most studies strongly suggest that these natural products could be promising for use in biocompatible sunscreens and may represent an alternative eco-friendly approach to protect humans against UV-induced skin damage

Metabolic Adaptations to Marine Environments: Molecular Diversity and Evolution of Ovothiol Biosynthesis in Bacteria

Ovothiols are sulfur-containing amino acids synthesized by marine invertebrates, protozoans, and bacteria. They act as pleiotropic molecules in signaling 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 distribution and molecular diversification in nature. In this work, we conducted genomic and metagenomics data mining to investigate the distribution and diversification of ovothiol biosynthetic enzymes in Bacteria. We identified the bacteria endowed with this secondary metabolic pathway, described their taxonomy, habitat and biotic interactions in order to provide insight into their adaptation to specific environments. We report that OvoA and OvoB are mostly encountered in marine aerobic Proteobacteria, some of them establishing symbiotic or parasitic relationships with other organisms. We identified a horizontal gene transfer event of OvoB from Bacteroidetes living in symbiosis with Hydrozoa. Our search within the Ocean Gene Atlas revealed the occurrence of ovothiol biosynthetic genes in Proteobacteria living in a wide range of pelagic and highly oxygenated environments. Finally, we tracked the evolutionary history of ovothiol biosynthesis from marine bacteria to unicellular eukaryotes and metazoans. Our analysis provides new conceptual elements to unravel the evolutionary and ecological significance of ovothiol biosynthesis

A Survey on the Distribution of Ovothiol and ovoA Gene Expression in Different Tissues and Cells: A Comparative Analysis in Sea Urchins and Mussels

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 environmental stressors, new evidence suggests that they can also act as pheromones and participate in fundamental biological processes such as embryogenesis. To get further insight into the biological roles of ovothiols, we compared ovothiol biosynthesis in the sea urchin Paracentrotus lividus and in the mussel Mytilus galloprovincialis, the two species that represent the richest sources of these compounds among marine invertebrates. Ovothiol content was measured in different tissues and in the immune cells from both species and the expression levels of ovoA, the gene responsible for ovothiol biosynthesis, was inferred from publicly available transcriptomes. A comparative analysis of ovothiol biosynthesis in the two species allowed the identification of the tissues and cells synthesizing the metabolite and highlighted analogies and differences between sea urchins and mussels. By improving our knowledge on the biological roles of ovothiols and pointing out the existence of sustainable natural sources for their isolation, this study provides the basis for future biotechnological investigations on these valuable compounds

Comparative toxicities of selected rare earth elements: Sea urchin embryogenesis and fertilization damage with redox and cytogenetic effects

Background: Broad-rangingadverseeffectsareknownforrareearthelements(REE),yetonlyafew studies testedthetoxicityofseveralREE,promptingstudiesfocusingonmulti-parameterREEtoxicity. Methods: TrichloridesaltsofY,La,Ce,Nd,Sm,EuandGdweretestedin Paracentrotuslividus sea urchin embryos andspermfor:(1)developmentaldefectsineitherREE-exposedlarvaeorintheoffspringof REE-exposedsperm;(2)fertilizationsuccess;(3)mitoticanomaliesinREE-exposedembryosandinthe offspring ofREE-exposedsperm,and(4)reactiveoxygenspecies(ROS)formation,andmalondialdehyde (MDA)andnitricoxide(NO)levels. Results: REEs affected P.lividus larvaewithconcentration-relatedincreaseindevelopmentaldefects, 106 to 104 M, rankingas:Gd(III)4Y(III)4La(III)4Nd(III)≅Eu(III)4Ce(III)≅Sm(III). Nominalcon- centrations ofREEsaltswereconfirmed byinductivelycoupledplasmamassspectrometry(ICP-MS). Significant increasesinMDAlevels,ROSformation,andNOlevelswerefoundinREE-exposedembryos. Sperm exposuretoREEs(105 to 104 M) resultedinconcentration-relateddecreaseinfertilization success alongwithincreaseinoffspringdamage.Decreasedmitoticactivityandincreasedaberration ratesweredetectedinREE-exposedembryosandintheoffspringofREE-exposedsperm. Conclusion: REE-associated toxicityaffectingembryogenesis,fertilization,cytogeneticandredoxend- points showeddifferentactivitiesoftestedREEs.Damagetoearlylifestages,alongwithredoxandcy- togeneticanomaliesshouldbethefocusoffutureREEtoxicitystudies

Diclofenac-Induced Apoptosis in the Neuroblastoma Cell Line SH-SY5Y: Possible Involvement of the Mitochondrial Superoxide Dismutase

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 dismutase (SOD2) plays a crucial role in the defence against ROS, thus protecting against several apoptotic stimuli. Diclofenac decreased the protein levels and the enzymatic activity of SOD2, without any significant impairment of the corresponding mRNA levels in the SH-SY5Y extracts. When cells were incubated with an archaeal exogenous thioredoxin, an attenuation of the diclofenac-induced apoptosis was observed, together with an increase of SOD2 protein levels. Furthermore, diclofenac impaired the mitochondrial membrane potential, leading to a release of cytochrome c. These data suggest that mitochondria are involved in the diclofenac-induced apoptosis of SH-SY5Y cells and point to a possible role of SOD2 in this process

X-ray polarimetry reveals the magnetic field topology on sub-parsec scales in Tycho's supernova remnant

Supernova remnants are commonly considered to produce most of the Galactic cosmic rays via diffusive shock acceleration. However, many questions about the physical conditions at shock fronts, such as the magnetic-field morphology close to the particle acceleration sites, remain open. Here we report the detection of a localized polarization signal from some synchrotron X-ray emitting regions of Tycho's supernova remnant made by the Imaging X-ray Polarimetry Explorer. The derived polarization degree of the X-ray synchrotron emission is 9+/-2% averaged over the whole remnant, and 12+/-2% at the rim, higher than the 7-8% polarization value observed in the radio band. In the west region the polarization degree is 23+/-4%. The X-ray polarization degree in Tycho is higher than for Cassiopeia A, suggesting a more ordered magnetic-field or a larger maximum turbulence scale. The measured tangential polarization direction corresponds to a radial magnetic field, and is consistent with that observed in the radio band. These results are compatible with the expectation of turbulence produced by an anisotropic cascade of a radial magnetic-field near the shock, where we derive a magnetic-field amplification factor of 3.4+/-0.3. The fact that this value is significantly smaller than those expected from acceleration models is indicative of highly anisotropic magnetic-field turbulence, or that the emitting electrons either favor regions of lower turbulence, or accumulate close to where the magnetic-field orientation is preferentially radially oriented due to hydrodynamical instabilities.Comment: 31 pages, 7 figures, 3 tables. Accepted for publication in ApJ. Revised versio

Observations of 4U 1626-67 with the Imaging X-ray Polarimetry Explorer

We present measurements of the polarization of X-rays in the 2-8 keV band from the pulsar in the ultracompact low mass X-ray binary 4U1626-67 using data from the Imaging X-ray Polarimetry Explorer (IXPE). The 7.66 s pulsations were clearly detected throughout the IXPE observations as well as in the NICER soft X-ray observations, which we use as the basis for our timing analysis and to constrain the spectral shape over 0.4-10 keV energy band. Chandra HETGS high-resolution X-ray spectra were also obtained near the times of the IXPE observations for firm spectral modeling. We find an upper limit on the pulse-averaged linear polarization of <4% (at 95% confidence). Similarly, there was no significant detection of polarized flux in pulse phase intervals when subdividing the bandpass by energy. However, spectropolarimetric modeling over the full bandpass in pulse phase intervals provide a marginal detection of polarization of the power-law spectral component at the 4.8 +/- 2.3% level (90% confidence). We discuss the implications concerning the accretion geometry onto the pulsar, favoring two-component models of the pulsed emission.Comment: 19 pages, 7 figures, 7 tables; accepted for publication in the Astrophysical Journa

IXPE and XMM-Newton observations of the Soft Gamma Repeater SGR 1806-20

Recent observations with the Imaging X-ray Polarimetry Explorer (IXPE) of two anomalous X-ray pulsars provided evidence that X-ray emission from magnetar sources is strongly polarized. Here we report on the joint IXPE and XMM-Newton observations of the soft {\gamma}-repeater SGR 1806-20. The spectral and timing properties of SGR 1806-20 derived from XMM-Newton data are in broad agreement with previous measurements; however, we found the source at an all-time-low persistent flux level. No significant polarization was measured apart from the 4-5 keV energy range, where a probable detection with PD=31.6\pm 10.5% and PA=-17.6\pm 15 deg was obtained. The resulting polarization signal, together with the upper limits we derive at lower and higher energies 2-4 and 5-8 keV, respectively) is compatible with a picture in which thermal radiation from the condensed star surface is reprocessed by resonant Compton scattering in the magnetosphere, similar to what proposed for the bright magnetar 4U 0142+61.Comment: 11 pages, 3 figures, accepted for publication in Ap