scholarly journals What makes a fertile sperm? Unique molecular attributes of stallion fertility

Reproduction ◽  
2019 ◽  
Vol 158 (4) ◽  
pp. R125-R137 ◽  
Author(s):  
Róisín A Griffin ◽  
Mark Baker ◽  
Robert John Aitken ◽  
Aleona Swegen ◽  
Zamira Gibb
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Breeding Season ◽  
Molecular Mechanisms ◽  
Relative Importance ◽  
Accurate Assessment ◽  
Functional Competence ◽  
Thoroughbred Horse ◽  
Livestock Species ◽  
Horse Breeding

Stallions experience lower per-cycle conception rates compared to other livestock species, largely because they are selected for breeding based on athletic prowess and not reproductive fitness. Mares are seasonal breeders, and pregnancies cannot be detected until 10–14 days post cover via transrectal ultrasonography. This means the detection of stallion fertility fluctuations is delayed by at least 2 weeks, which within the short breeding season employed by the thoroughbred horse breeding industry, can prove quite costly. For these reasons, there is increased demand for robust laboratory assays aimed at the accurate assessment of stallion fertility. This paper reviews our existing knowledge concerning the molecular mechanisms that underpin the functional competence of stallion spermatozoa, highlighting the relative importance of oxidative stress, DNA damage, sperm proteomics and RNA profile. We also consider the way in which fundamental improvements in our understanding of stallion sperm biology are informing the identification and development of possible biomarkers of fertility and thus avenues for the development of specific assays for fertility prediction.

scholarly journals Sirtuins: Molecular Traffic Lights in the Crossroad of Oxidative Stress, Chromatin Remodeling, and Transcription

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Ramkumar Rajendran ◽  
Richa Garva ◽  
Marija Krstic-Demonacos ◽  
Constantinos Demonacos
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Transcriptional Regulation ◽  
Histone Deacetylases ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Class Iii ◽  
Nonhistone Proteins ◽  
Traffic Lights ◽  
Major Mechanism

Transcription is regulated by acetylation/deacetylation reactions of histone and nonhistone proteins mediated by enzymes called KATs and HDACs, respectively. As a major mechanism of transcriptional regulation, protein acetylation is a key controller of physiological processes such as cell cycle, DNA damage response, metabolism, apoptosis, and autophagy. The deacetylase activity of class III histone deacetylases or sirtuins depends on the presence of NAD+(nicotinamide adenine dinucleotide), and therefore, their function is closely linked to cellular energy consumption. This activity of sirtuins connects the modulation of chromatin dynamics and transcriptional regulation under oxidative stress to cellular lifespan, glucose homeostasis, inflammation, and multiple aging-related diseases including cancer. Here we provide an overview of the recent developments in relation to the diverse biological activities associated with sirtuin enzymes and stress responsive transcription factors, DNA damage, and oxidative stress and relate the involvement of sirtuins in the regulation of these processes to oncogenesis. Since the majority of the molecular mechanisms implicated in these pathways have been described for Sirt1, this sirtuin family member is more extensively presented in this paper.

scholarly journals Tellurite Promotes Stress Granules and Nuclear SG-Like Assembly in Response to Oxidative Stress and DNA Damage

2021 ◽  
Vol 9 ◽  
Author(s):  
Aracelly Gaete-Argel ◽  
Felipe Velásquez ◽  
Chantal L. Márquez ◽  
Barbara Rojas-Araya ◽  
Constanza Bueno-Nieto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Molecular Mechanisms ◽  
Stress Granules ◽  
Cellular Stress Response ◽  
Industrial Manufacturing ◽  
The Past ◽  
Γh2ax Foci ◽  
Bona Fide ◽  
And Oxidative Stress

Tellurium oxyanion, tellurite (TeO3–2), is a highly toxic compound for many organisms. Its presence in the environment has increased over the past years due to industrial manufacturing processes and has been associated with adverse effects on human health. Although tellurite induces the phosphorylation of eIF2α, DNA damage and oxidative stress, the molecular mechanisms related to the cellular responses to tellurite-induced stress are poorly understood. In this work, we evaluated the ability of tellurite to induce phosphorylation of eIF2α, stress granules (SGs) assembly and their relationship with DNA damage in U2OS cells. We demonstrate that tellurite promotes the assembly of bona fide cytoplasmic SGs. Unexpectedly, tellurite also induces the assembly of nuclear SGs. Interestingly, we observed that the presence of tellurite-induced nuclear SGs correlates with γH2AX foci. However, although H2O2 also induce DNA damage, no nuclear SGs were observed. Our data show that tellurite promotes the assembly of cytoplasmic and nuclear SGs in response to oxidative stress and DNA damage, revealing a new aspect of cellular stress response mediated by the assembly of nuclear stress granules.

scholarly journals DNA Damage Response

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Melinda Duer ◽  
Andrew M. Cobb ◽  
Catherine M. Shanahan
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Vascular Calcification ◽  
Dna Damage Response ◽  
Healthy Aging ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Damage Response ◽  
Novel Treatment Strategies ◽  
Tissue Aging

Vascular calcification is a ubiquitous pathology of aging. Oxidative stress, persistent DNA damage, and senescence are major pathways driving both cellular and tissue aging, and emerging evidence suggests that these pathways are activated, and even accelerated, in patients with vascular calcification. The DNA damage response—a complex signaling platform that maintains genomic integrity—is induced by oxidative stress and is intimately involved in regulating cell death and osteogenic differentiation in both bone and the vasculature. Unexpectedly, a posttranslational modification, PAR (poly[ADP-ribose]), which is a byproduct of the DNA damage response, initiates biomineralization by acting to concentrate calcium into spheroidal structures that can nucleate apatitic mineral on the ECM (extracellular matrix). As we start to dissect the molecular mechanisms driving aging-associated vascular calcification, novel treatment strategies to promote healthy aging and delay pathological change are being unmasked. Drugs targeting the DNA damage response and senolytics may provide new avenues to tackle this detrimental and intractable pathology.

scholarly journals Fetotoxicity of Nanoparticles: Causes and Mechanisms

Nanomaterials ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 791
Author(s):  
Chuanfeng Teng ◽  
Cuijuan Jiang ◽  
Sulian Gao ◽  
Xiaojing Liu ◽  
Shumei Zhai
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Physicochemical Properties ◽  
Molecular Mechanisms ◽  
Consumer Products ◽  
Placental Barrier ◽  
Factors Associated ◽  
Pathological Conditions ◽  
Susceptible Populations ◽  
Maternal Fetal Interface

The application of nanoparticles in consumer products and nanomedicines has increased dramatically in the last decade. Concerns for the nano-safety of susceptible populations are growing. Due to the small size, nanoparticles have the potential to cross the placental barrier and cause toxicity in the fetus. This review aims to identify factors associated with nanoparticle-induced fetotoxicity and the mechanisms involved, providing a better understanding of nanotoxicity at the maternal–fetal interface. The contribution of the physicochemical properties of nanoparticles (NPs), maternal physiological, and pathological conditions to the fetotoxicity is highlighted. The underlying molecular mechanisms, including oxidative stress, DNA damage, apoptosis, and autophagy are summarized. Finally, perspectives and challenges related to nanoparticle-induced fetotoxicity are also discussed.

scholarly journals PTEN Reduced UVB-Mediated Apoptosis in Retinal Pigment Epithelium Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jia He ◽  
Chongde Long ◽  
Zixin Huang ◽  
Xin Zhou ◽  
Xielan Kuang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Molecular Mechanisms ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Age Related ◽  
Induced Apoptosis

Age-related macular degeneration (AMD) is a leading cause of blindness and progressive loss of central vision in the elderly population. The important factor of AMD pathogenesis is the degeneration of retinal pigment epithelial (RPE) cells by oxidative stress. Inactivation of PTEN can disrupt intercellular adhesion in the RPE cells, but the mechanism of oxidative stress is less known. Here we presented evidence that UVB-mediated oxidative stress induced apoptosis in ARPE-19 cells. Downregulation of the expression of PTEN in UVB-irradiative RPE cells triggered DNA damage and increased the level of UVB-induced apoptosis by activating p53-dependent pathway. However, overexpression of PTEN increased cell survival by suppressing p-H2A in response to DNA damage and apoptosis. When using Pifithrin-α(one of p53 inhibitors), the level of p53-dependent apoptosis was significantly lower than untreated, which suggested that p53 was possibly involved in PTEN-dependent apoptosis. Thus, it elucidated the molecular mechanisms of UVB-induced damage in RPE cells and may offer an alternative therapeutic target in dry AMD.

scholarly journals Modulation of Oxidative Status by Normoxia and Hypoxia on Cultures of Human Dermal Fibroblasts: How Does It Affect Cell Aging?

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Elisabetta Damiani ◽  
Francesca Brugè ◽  
Ilenia Cirilli ◽  
Fabio Marcheggiani ◽  
Fabiola Olivieri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Oxygen Tension ◽  
Molecular Mechanisms ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Cellular Aging ◽  
Cell Aging ◽  
Ros Production ◽  
Human Dermal Fibroblasts

Reactive oxygen species (ROS) production in the skin is among the highest compared to other organs, and a clear correlation exists between ROS production and skin aging. Many attempts are underway to reduce oxidative stress in the skin by topical treatment or supplementation with antioxidants/cosmeceuticals, and cultures of human dermal fibroblasts (HDF) are widely used for these studies. Here, we examined the influence of oxygen tension on cell aging in HDF and how this impacted ROS production, the enzymatic and nonenzymatic antioxidant response system, and the efficacy of this defense system in limiting DNA damage and in modulating gene expression of proteins involved in the extracellular matrix, linked to skin aging. We investigated a selection of parameters that represent and reflect the behavior of cellular responses to aging and oxygen tension. Serial passaging of HDF under normoxia (21%) and hypoxia (5%) leads to cell aging as confirmed by β-galactosidase activity, p16 expression, and proliferation rate. However, in HDF under 21% O2, markers of aging were significantly increased compared to those under 5% O2 at matched cell passages despite having lower levels of intracellular ROS and higher levels of CoQ10, total GSH, SOD1, SOD3, and mitochondrial superoxide anion. miRNA-181a, which is known to be upregulated in HDF senescence, was also analyzed, and indeed, its expression was significantly increased in old cells at 21% O2 compared to those at 5% O2. Upregulation of MMP1 and downregulation of COL1A1 along with increased DNA damage were also observed under 21% O2 vs 5% O2. The data highlight that chronic exposure to atmospheric 21% O2 is able to trigger hormetic adaptive responses in HDF that however fail, in the long term, to prevent cellular aging. This information could be useful in further investigating molecular mechanisms involved in adaptation of skin fibroblasts to oxidative stress and may provide useful hints in addressing antiaging strategies.

scholarly journals ‘Liver let die’: oxidative DNA damage and hepatotropic viruses

2014 ◽  
Vol 95 (5) ◽  
pp. 991-1004 ◽  
Author(s):  
Martin R. Higgs ◽  
Philippe Chouteau ◽  
Hervé Lerat
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cellular Response ◽  
Oxidative Dna Damage ◽  
Molecular Mechanisms ◽  
Large Body ◽  
Clinical Importance ◽  
Dna Lesions ◽  
Chronic Infections ◽  
The Impact

Chronic infections by the hepatotropic viruses hepatitis B virus (HBV) and hepatitis C virus (HCV) are major risk factors for the development of hepatocellular carcinoma (HCC). It is estimated that more than 700 000 individuals per year die from HCC, and around 80 % of HCC is attributable to HBV or HCV infection. Despite the clear clinical importance of virus-associated HCC, the underlying molecular mechanisms remain largely elusive. Oxidative stress, in particular DNA lesions associated with oxidative damage, play a major contributory role in carcinogenesis, and are strongly linked to the development of many cancers, including HCC. A large body of evidence demonstrates that both HBV and HCV induce hepatic oxidative stress, with increased oxidative DNA damage being observed both in infected individuals and in murine models of infection. Here, we review the impact of HBV and HCV on the incidence and repair of oxidative DNA damage. We begin by giving a brief overview of oxidative stress and the repair of DNA lesions induced by oxidative stress. We then review in detail the evidence surrounding the mechanisms by which both viruses stimulate oxidative stress, before focusing on how the viral proteins themselves may perturb the cellular response to oxidative DNA damage, impacting upon genome stability and thus hepatocarcinogenesis.

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