Discovery of the Involvement in DNA Oxidative Damage of Human Sperm Nuclear Basic Proteins of Healthy Young Men Living in Polluted Areas

Lettieri, Gennaro; D’Agostino, Giovanni; Mele, Elena; Cardito, Carolina; Esposito, Rosa; Cimmino, Annalinda; Giarra, Antonella; Trifuoggi, Marco; Raimondo, Salvatore; Notari, Tiziana; Febbraio, Ferdinando; Montano, Luigi; Piscopo, Marina

doi:10.3390/ijms21124198

Cited by 67 publications

(78 citation statements)

References 65 publications

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“…GSK-3 may also contribute to identifying markers for DNA damage since its substrates are regulated via the PI3K-AKT-GSK-3 ( Figure 4 b) signaling network [ 39 ]. In fact, DNA integrity analysis is a better diagnostic and prognostic marker of sperm reproductive potential, for example, changes in nuclear basic proteins in human sperm exposure to heavy metals were recently explored [ 40 ] to link to DNA damage. The current study aimed to explore translational protein markers specific to the process of capacitation to mimic sperm cells passing to the uterus.…”

Section: Discussionmentioning

confidence: 99%

Phosphoproteomics and Bioinformatics Analyses Reveal Key Roles of GSK-3 and AKAP4 in Mouse Sperm Capacitation

Syifa

Yang

et al. 2020

IJMS

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Protein phosphorylation can induce signal transduction to change sperm motility patterns during sperm capacitation. However, changes in the phosphorylation of sperm proteins in mice are still incompletely understood. Here, capacitation-related phosphorylation in mouse sperms were firstly investigated by label-free quantitative (LFQ) phosphoproteomics coupled with bioinformatics analysis using ingenuity pathway analysis (IPA) methods such as canonical pathway, upstream regulator, and network analysis. Among 1632 phosphopeptides identified at serine, threonine, and tyrosine residues, 1050 novel phosphosites, corresponding to 402 proteins, were reported. Gene heatmaps for IPA canonical pathways showed a novel role for GSK-3 in GP6 signaling pathways associated with capacitation for 60 min. At the same time, the reduction of the abundant isoform-specific GSK-3α expression was shown by western blot (WB) while the LFQ pY of this isoform slightly decreased and then increased. The combined results from WB and LFQ methods explain the less inhibitory phosphorylation of GSK-3α during capacitation and also support the predicted increases in its activity. In addition, pAKAP4 increased at the Y156 site but decreased at the Y811 site in a capacitated state, even though IPA network analysis and WB analysis for overall pAKAP revealed upregulated trends. The potential roles of GSK-3 and AKAP4 in fertility are discussed.

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Section: Discussionmentioning

confidence: 99%

Phosphoproteomics and Bioinformatics Analyses Reveal Key Roles of GSK-3 and AKAP4 in Mouse Sperm Capacitation

Syifa

Yang

et al. 2020

IJMS

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“…HDACs are very important to convert chromatin states and transition histones-protamines in human spermatozoa. GasPhos could be used to study the effects of heavy metals that lead to alterations in the reproductive health of marine organisms and humans [46][47][48].…”

Section: Discussionmentioning

confidence: 99%

GasPhos: Protein Phosphorylation Site Prediction Using a New Feature Selection Approach with a GA-Aided Ant Colony System

Chen

Liao

Chang

et al. 2020

IJMS

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Protein phosphorylation is one of the most important post-translational modifications, and many biological processes are related to phosphorylation, such as DNA repair, transcriptional regulation and signal transduction and, therefore, abnormal regulation of phosphorylation usually causes diseases. If we can accurately predict human phosphorylation sites, this could help to solve human diseases. Therefore, we developed a kinase-specific phosphorylation prediction system, GasPhos, and proposed a new feature selection approach, called Gas, based on the ant colony system and a genetic algorithm and used performance evaluation strategies focused on different kinases to choose the best learning model. Gas uses the mean decrease Gini index (MDGI) as a heuristic value for path selection and adopts binary transformation strategies and new state transition rules. GasPhos can predict phosphorylation sites for six kinases and showed better performance than other phosphorylation prediction tools. The disease-related phosphorylated proteins that were predicted with GasPhos are also discussed. Finally, Gas can be applied to other issues that require feature selection, which could help to improve prediction performance. GasPhos is available at http://predictor.nchu.edu.tw/GasPhos.

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“…As a matter of fact, sperm cells are highly sensitive to the pro-oxidant effects of environmental pollutants, due to the limited volume of the cytoplasmic space, with less antioxidant defence, and sperm membrane lipids are target of ROS 57 . In this regard, we recently reported that male gametes are the most sensitive cells to the accumulation of damaged DNA and showed, through molecular investigations, that the sperm nuclear basic proteins from samples of men living in polluted areas have a new and unexpected behaviour, resulting involved in DNA oxidative damage 58 . The COVID-19 CFR map of the most important outbreaks in the world areas presenting, in recent decades, a negative trend in sperm quality, together with the average annual levels of PM 10 , PM 2.5 and NO 2 , shows a certain overlapping (figure 1).…”

Section: Sperm Decline In Polluted Areasmentioning

confidence: 99%

Semen Quality as a Potential Susceptibility Indicator to SARS-CoV-2 Insults in Polluted Areas<strong> </strong>

Montano¹,

Bonapace²,

Donato³

et al. 2020

Preprint

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High levels of air pollution can contribute to high rate of the COVID-19 outbreaks. Air pollutants induce oxidative stress, inflammatory process, immune imbalance and coagulation at systemic level, making the organism susceptible to complications caused by various pathogens, including viruses, resulting in a possible important damage co-factor. Sperm cells are highly sensitive to the pro-oxidant effects of environmental pollutants, and represent an important alarm bell indicating how the burden of environmental pressure in a certain area is becoming increasingly unsustainable. We underline that overlapping among maps of case fatality rate of COVID-19, male infertility rate and air pollution can be a challenging idea to understand the dynamics of the virus impact, considering semen quality that is an early and sensitive environmental marker, and could be a potential susceptibility indicator to viral insults (including SARS-CoV-2 ) in heavily polluted areas. So that, assessing the burden of environmental exposure of a given population and its potential susceptibility to insults through early biological stress indicators able to predict the probability, nature and magnitude for the adverse effects is a major public health challenge.

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Discovery of the Involvement in DNA Oxidative Damage of Human Sperm Nuclear Basic Proteins of Healthy Young Men Living in Polluted Areas

Cited by 67 publications

References 65 publications

Phosphoproteomics and Bioinformatics Analyses Reveal Key Roles of GSK-3 and AKAP4 in Mouse Sperm Capacitation

Phosphoproteomics and Bioinformatics Analyses Reveal Key Roles of GSK-3 and AKAP4 in Mouse Sperm Capacitation

GasPhos: Protein Phosphorylation Site Prediction Using a New Feature Selection Approach with a GA-Aided Ant Colony System

Semen Quality as a Potential Susceptibility Indicator to SARS-CoV-2 Insults in Polluted Areas<strong> </strong>

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