Singlet oxygen (1O2) is a biologically relevant reactive oxygen species capable of efficiently reacting with cellular constituents. The resulting oxidatively generated damage to nucleic acids, ...membrane unsaturated lipids, and protein components has been shown to be implicated in several diseases, including arthritis, cataracts, and skin cancer. Singlet oxygen may be endogenously produced, among various possibilities, by myeloperoxidase, an enzyme implicated in inflammation processes, and also efficiently in skin by the UVA component of solar radiation through photosensitization reactions. Emphasis is placed in this Review on the description of the main oxidation reactions initiated by 1O2 and the resulting modifications within key cellular targets, including guanine for nucleic acids, unsaturated lipids, and targeted amino acids. Most of these reactions give rise to peroxides and dioxetanes, whose formation has been rationalized in terms of 4+2 cycloaddition and 1,2-cycloaddition with dienes + olefins, respectively. The use of 18O-labeled thermolabile endoperoxides as a source of 18O-labeled 1O2 has been applied to study mechanistic aspects and preferential targets of 1O2 in biological systems. A relevant major topic deals with the search for the molecular signature of the 1O2 formation in targeted biomolecules within cells. It may be anticipated that 18O-labeled 1O2 and labeled peroxides in association with sensitive mass spectrometric methods should constitute powerful tools for this purpose.
Background Our knowledge of plant beneficial bacteria in the rhizosphere is rapidly expanding due to intense interest in utilizing these types of microbes in agriculture. Laboratory and field studies ...consistently document the growth, health and protective benefits conferred to plants by applying plant growth promoting rhizobacteria (PGPR). PGPR exert their influence on other species, including plants, in the rhizosphere by producing a wide array of extracellular molecules for communication and defense. Scope The types of PGPR molecular products are characteristically diverse, and the mechanisms by which they are acting on the plant are only beginning to be understood. While plants may contribute to shape their microbiome, it is these bacterial products which induce beneficial responses in plants. PGPR extracellular products can directly stimulate plant genetic and molecular pathways, leading to increases in plant growth and induction of plant resistance and tolerance. This review will discuss known PGPR-derived molecules, and how these products are implicated in inducing plant beneficial outcomes through complex plant response mechanisms. Conclusions In order to move PGPR research to the next level, it will be important to describe and document the genetic and molecular mechanisms employed in these interactions. In this way, we will be able to restructure and harness these mechanisms in a way that allows for broad-based applications in agriculture. A greater depth of understanding of how these PGPR molecules are acting on the plant will allow more effective development of rhizobacterial applications in the field.
Protecting human skin from sun exposure is a complex issue that involves unclear aspects of the interaction between light and tissue. A persistent misconception is that visible light is safe for the ...skin, although several lines of evidence suggest otherwise. Here, we show that visible light can damage melanocytes through melanin photosensitization and singlet oxygen (1O2) generation, thus decreasing cell viability, increasing membrane permeability, and causing both DNA photo-oxidation and necro-apoptotic cell death. UVA (355 nm) and visible (532 nm) light photosensitize 1O2 with similar yields, and pheomelanin is more efficient than eumelanin at generating 1O2 and resisting photobleaching. Although melanin can protect against the cellular damage induced by UVB, exposure to visible light leads to pre-mutagenic DNA lesions (i.e., Fpg- and Endo III-sensitive modifications); these DNA lesions may be mutagenic and may cause photoaging, as well as other health problems, such as skin cancer.
Intermittent fasting (IF) is a dietary intervention often used as an alternative to caloric restriction (CR) and characterized by 24 hour cycles alternating ad libitum feeding and fasting. Although ...the consequences of CR are well studied, the effects of IF on redox status are not. Here, we address the effects of IF on redox state markers in different tissues in order to uncover how changes in feeding frequency alter redox balance in rats. IF rats displayed lower body mass due to decreased energy conversion efficiency. Livers in IF rats presented increased mitochondrial respiratory capacity and enhanced levels of protein carbonyls. Surprisingly, IF animals also presented an increase in oxidative damage in the brain that was not related to changes in mitochondrial bioenergetics. Conversely, IF promoted a substantial protection against oxidative damage in the heart. No difference in mitochondrial bioenergetics or redox homeostasis was observed in skeletal muscles of IF animals. Overall, IF affects redox balance in a tissue-specific manner, leading to redox imbalance in the liver and brain and protection against oxidative damage in the heart.
Critical to the design and assessment of interventions for enteropathy and its developmental consequences in children living in impoverished conditions are non-invasive biomarkers that can detect ...intestinal damage and predict its effects on growth and development. We therefore assessed fecal, urinary and systemic biomarkers of enteropathy and growth predictors in 375 6-26 month-old children with varying degrees of malnutrition (stunting or wasting) in Northeast Brazil. 301 of these children returned for followup anthropometry after 2-6m. Biomarkers that correlated with stunting included plasma IgA anti-LPS and anti-FliC, zonulin (if >12m old), and intestinal FABP (I-FABP, suggesting prior barrier disruption); and with citrulline, tryptophan and with lower serum amyloid A (SAA) (suggesting impaired defenses). In contrast, subsequent growth was predicted in those with higher fecal MPO or A1AT and also by higher L/M, plasma LPS, I-FABP and SAA (showing intestinal barrier disruption and inflammation). Better growth was predicted in girls with higher plasma citrulline and in boys with higher plasma tryptophan. Interactions were also seen with fecal MPO and neopterin in predicting subsequent growth impairment. Biomarkers clustered into markers of 1) functional intestinal barrier disruption and translocation, 2) structural intestinal barrier disruption and inflammation and 3) systemic inflammation. Principle components pathway analyses also showed that L/M with %L, I-FABP and MPO associate with impaired growth, while also (like MPO) associating with a systemic inflammation cluster of kynurenine, LBP, sCD14, SAA and K/T. Systemic evidence of LPS translocation associated with stunting, while markers of barrier disruption or repair (A1AT and Reg1 with low zonulin) associated with fecal MPO and neopterin. We conclude that key noninvasive biomarkers of intestinal barrier disruption, LPS translocation and of intestinal and systemic inflammation can help elucidate how we recognize, understand, and assess effective interventions for enteropathy and its growth and developmental consequences in children in impoverished settings.
Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of upper and lower motor neurons leading to muscle paralysis and death. While a link between dysregulated lipid metabolism and ...ALS has been proposed, lipidome alterations involved in disease progression are still understudied. Using a rodent model of ALS overexpressing mutant human Cu/Zn-superoxide dismutase gene (SOD1-G93A), we performed a comparative lipidomic analysis in motor cortex and spinal cord tissues of SOD1-G93A and WT rats at asymptomatic (~70 days) and symptomatic stages (~120 days). Interestingly, lipidome alterations in motor cortex were mostly related to age than ALS. In contrast, drastic changes were observed in spinal cord of SOD1-G93A 120d group, including decreased levels of cardiolipin and a 6-fold increase in several cholesteryl esters linked to polyunsaturated fatty acids. Consistent with previous studies, our findings suggest abnormal mitochondria in motor neurons and lipid droplets accumulation in aberrant astrocytes. Although the mechanism leading to cholesteryl esters accumulation remains to be established, we postulate a hypothetical model based on neuroprotection of polyunsaturated fatty acids into lipid droplets in response to increased oxidative stress. Implicated in the pathology of other neurodegenerative diseases, cholesteryl esters appear as attractive targets for further investigations.
In pathogenic fungi, melanin contributes to virulence, allowing tissue invasion and inactivation of the plant defence system, but has never been implicated as a factor for host cell death, or as a ...light-activated phytotoxin. Our research shows that melanin synthesized by the fungal banana pathogen Mycosphaerella fijiensis acts as a virulence factor through the photogeneration of singlet molecular oxygen O2 (1Δg). Using analytical tools, including elemental analysis, ultraviolet/infrared absorption spectrophometry and MALDI-TOF mass spectrometry analysis, we characterized both pigment content in mycelia and secreted to the culture media as 1,8-dihydroxynaphthalene (DHN)-melanin type compound. This is sole melanin-type in M. fijiensis. Isolated melanins irradiated with a Nd:YAG laser at 532 nm produced monomol light emission at 1270 nm, confirming generation of O2 (1Δg), a highly reactive oxygen specie (ROS) that causes cellular death by reacting with all cellular macromolecules. Intermediary polyketides accumulated in culture media by using tricyclazole and pyroquilon (two inhibitors of DHN-melanin synthesis) were identified by ESI-HPLC-MS/MS. Additionally, irradiation at 532 nm of that mixture of compounds and whole melanized mycelium also generated O2 (1Δg). A pigmented-strain generated more O2 (1Δg) than a strain with low melanin content. Banana leaves of cultivar Cavendish, naturally infected with different stages of black Sigatoka disease, were collected from field. Direct staining of the naturally infected leaf tissues showed the presence of melanin that was positively correlated to the disease stage. We also found hydrogen peroxide (H2O2) but we cannot distinguish the source. Our results suggest that O2 (1Δg) photogenerated by DHN-melanin may be involved in the destructive effects of Mycosphaerella fijiensis on banana leaf tissues. Further studies are needed to fully evaluate contributions of melanin-mediated ROS to microbial pathogenesis.
In this review article, emphasis is placed on the critical survey of available data concerning modified nucleobase and 2-deoxyribose products that have been identified in cellular DNA following ...exposure to a wide variety of oxidizing species and agents including, hydroxyl radical, one-electron oxidants, singlet oxygen, hypochlorous acid and ten-eleven translocation enzymes. In addition, information is provided about the generation of secondary oxidation products of 8-oxo-7,8-dihydroguanine and nucleobase addition products with reactive aldehydes arising from the decomposition of lipid peroxides. It is worth noting that the different classes of oxidatively generated DNA damage that consist of single lesions, intra- and interstrand cross-links were unambiguously assigned and quantitatively detected on the basis of accurate measurements involving in most cases high performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry. The reported data clearly show that the frequency of DNA lesions generated upon severe oxidizing conditions, including exposure to ionizing radiation is low, at best a few modifications per 106 normal bases. Application of accurate analytical measurement methods has also allowed the determination of repair kinetics of several well-defined lesions in cellular DNA that however concerns so far only a restricted number of cases.
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•HPLC based methods are appropriate for monitoring oxidatively damage to DNA.•Single base lesions, intra- and interstrand cross-links were identified in cellular DNA.•Other modifications included halogenated bases and adducts with reactive aldehydes.•Paucity of reliable data on the base excision repair of oxidized bases in cells.
Chloride is one of the main factors responsible for damages related to the corrosion of the concrete reinforcement in marine environments. It is known that this mechanism of degradation is directly ...related to environmental variables. Within this context, it can be inserted the global climate change. This paper deals with the effects of temperature and relative humidity changes on the service life of concrete structures affected by chloride attack. This way, three situations of environmental aggressiveness were simulated: past, current, and future. Then, models for predicting the chlorides penetration were analyzed to the three selected situations. So, a practical methodology is presented, and the results are consistent with the literature data. Among the results, it can be noted that changes in temperature and relative humidity identified in a period of 100 years were responsible for a reduction from 7.8 to 10.2 years of service life. Most standards provide a design service life of 50 years for reinforced concrete structures.
Enteroaggregative E. coli (EAEC) have been associated with mildly inflammatory diarrhea in outbreaks and in travelers and have been increasingly recognized as enteric pathogens in young children with ...and without overt diarrhea. We examined the risk factors for EAEC infections and their associations with environmental enteropathy biomarkers and growth outcomes over the first two years of life in eight low-resource settings of the MAL-ED study.
EAEC infections were detected by PCR gene probes for aatA and aaiC virulence traits in 27,094 non-diarrheal surveillance stools and 7,692 diarrheal stools from 2,092 children in the MAL-ED birth cohort. We identified risk factors for EAEC and estimated the associations of EAEC with diarrhea, enteropathy biomarker concentrations, and both short-term (one to three months) and long-term (to two years of age) growth.
Overall, 9,581 samples (27.5%) were positive for EAEC, and almost all children had at least one detection (94.8%) by two years of age. Exclusive breastfeeding, higher enrollment weight, and macrolide use within the preceding 15 days were protective. Although not associated with diarrhea, EAEC infections were weakly associated with biomarkers of intestinal inflammation and more strongly with reduced length at two years of age (LAZ difference associated with high frequency of EAEC detections: -0.30, 95% CI: -0.44, -0.16).
Asymptomatic EAEC infections were common early in life and were associated with linear growth shortfalls. Associations with intestinal inflammation were small in magnitude, but suggest a pathway for the growth impact. Increasing the duration of exclusive breastfeeding may help prevent these potentially inflammatory infections and reduce the long-term impact of early exposure to EAEC.
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