Copper-induced apoptosis and autophagy through oxidative stress-mediated mitochondrial dysfunction in male germ cells

Abstract The efficiency of antioxidant defense system decreases with aging, thus resulting in high levels of reactive oxygen species (ROS) and DNA damage in spermatozoa. This damage can lead to genetic disorders in the offspring. There are limited studies investigating the effects of the total loss of antioxidants, such as superoxide dismutase-1 (SOD1), in male germ cells as they progress through spermatogenesis. In this study, we evaluated the effects of aging and removing SOD1 (in male germ cells of SOD1-null (Sod1−/−) mice) in order to determine the potential mechanism(s) of DNA damage in these cells. Immunohistochemical analysis showed an increase in lipid peroxidation and DNA damage in the germ cells of aged wild-type (WT) and Sod1−/− mice of all age. Immunostaining of OGG1, a marker of base excision repair (BER), increased in aged WT and young Sod1−/− mice. In contrast, immunostaining intensity of LIGIV and RAD51, markers of non-homologous end-joining (NHEJ) and homologous recombination (HR), respectively, decreased in aged and Sod1−/− mice. Gene expression analysis showed similar results with altered mRNA expression of these key DNA repair transcripts in pachytene spermatocytes and round spermatids of aged and Sod1−/− mice. Our study indicates that DNA repair pathway markers of BER, NHEJ, and HR are differentially regulated as a function of aging and oxidative stress in spermatocytes and spermatids, and aging enhances the repair response to increased oxidative DNA damage, whereas impairments in other DNA repair mechanisms may contribute to the increase in DNA damage caused by aging and the loss of SOD1.

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Mitochondrial Division Inhibitor 1 Attenuates Mitophagy in a Rat Model of Acute Lung Injury

BioMed Research International ◽

10.1155/2019/2193706 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Xu Luo ◽

Ruimeng Liu ◽

Zhihao Zhang ◽

Zhugui Chen ◽

Jian He ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Lung Injury ◽

Lung Injury ◽

Mitochondrial Dysfunction ◽

Cell Damage ◽

A549 Cells ◽

Oxygenation Index ◽

Lipid Peroxides ◽

Dry Weight ◽

Induced Apoptosis

The regulation of intracellular mitochondria degradation is mediated by mitophagy. While studies have shown that mitophagy can lead to mitochondrial dysfunction and cell damage, the role of Mdivi-1 and mitophagy remains unclear in acute lung injury (ALI) pathogenesis. In this study, we demonstrated that Mdivi-1, which is widely used as an inhibitor of mitophagy, ameliorated acute lung injury assessed by HE staining, pulmonary microvascular permeability assay, measurement of wet/dry weight (W/D) ratio, and oxygenation index (PaO2/FiO2) analysis. Then, the mitophagy related proteins were evaluated by western blot. The results indicated that LPS-induced activation of mitophagy was inhibited by Mdivi-1 treatment. In addition, we found that Mdivi-1 protected A549 cells against LPS-induced mitochondrial dysfunction. We also found that Mdivi-1 reduced pulmonary cell apoptosis in the LPS-challenged rats and protected pulmonary tissues from oxidative stress (represented by the content of superoxide dismutase, malondialdehyde and lipid peroxides in lung). Moreover, Mdivi-1 treatment ameliorated LPS-induced lung inflammatory response and cells recruitment. These findings indicate that Mdivi-1 mitigates LPS-induced apoptosis, oxidative stress, and inflammation in ALI, which may be associated with mitophagy inhibition. Thus, the inhibition of mitophagy may represent a potential therapy for treating ALI.

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Overexpression of peroxisomal testis-specific 1 protein induces germ cell apoptosis and leads to infertility in male mice

Molecular Biology of the Cell ◽

10.1091/mbc.e09-12-0993 ◽

2011 ◽

Vol 22 (10) ◽

pp. 1766-1779 ◽

Cited By ~ 16

Author(s):

Karina Kaczmarek ◽

Maja Studencka ◽

Andreas Meinhardt ◽

Krzysztof Wieczerzak ◽

Sven Thoms ◽

...

Keyword(s):

Cell Death ◽

Germ Cell ◽

Germ Cells ◽

Specific Gene ◽

Male Mice ◽

Terminal Part ◽

Male Germ Cells ◽

Germ Cell Apoptosis ◽

Induced Apoptosis

Peroxisomal testis-specific 1 gene (Pxt1) is the only male germ cell–specific gene that encodes a peroxisomal protein known to date. To elucidate the role of Pxt1 in spermatogenesis, we generated transgenic mice expressing a c-MYC-PXT1 fusion protein under the control of the PGK2 promoter. Overexpression of Pxt1 resulted in induction of male germ cells’ apoptosis mainly in primary spermatocytes, finally leading to male infertility. This prompted us to analyze the proapoptotic character of mouse PXT1, which harbors a BH3-like domain in the N-terminal part. In different cell lines, the overexpression of PXT1 also resulted in a dramatic increase of apoptosis, whereas the deletion of the BH3-like domain significantly reduced cell death events, thereby confirming that the domain is functional and essential for the proapoptotic activity of PXT1. Moreover, we demonstrated that PXT1 interacts with apoptosis regulator BAT3, which, if overexpressed, can protect cells from the PXT1-induced apoptosis. The PXT1-BAT3 association leads to PXT1 relocation from the cytoplasm to the nucleus. In summary, we demonstrated that PXT1 induces apoptosis via the BH3-like domain and that this process is inhibited by BAT3.

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Emodin Alleviates Hydrogen Peroxide-Induced Inflammation and Oxidative Stress via Mitochondrial Dysfunction by Inhibiting the PI3K/mTOR/GSK3β Pathway in Neuroblastoma SH-SY5Y Cells

BioMed Research International ◽

10.1155/2020/1562915 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Rui Li ◽

Wenzhou Liu ◽

Li Ou ◽

Feng Gao ◽

Min Li ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Cell Damage ◽

Neuroblastoma Cells ◽

Inflammatory Factors ◽

Protective Mechanism ◽

Human Neuroblastoma ◽

Induced Apoptosis

Emodin is an active monomer extracted from rhubarb root, which has many biological functions, including anti-inflammation, antioxidation, anticancer, and neuroprotection. However, the protective effect of emodin on nerve injury needs to be further elucidated. The purpose of this study is to investigate the effect of emodin on the neuroprotection and the special molecular mechanism. Here, the protective activity of emodin inhibiting H2O2-induced apoptosis and neuroinflammation as well as its molecular mechanisms was examined using human neuroblastoma cells (SH-SY5Y cells). The results showed that emodin significantly enhanced cell viability, reduced cell apoptosis and LDH release. Simultaneously, emodin downregulated H2O2-induced inflammatory factors, including IL-6, NO, and TNF-α, and alleviated H2O2-induced oxidative stress and mitochondrial dysfunction in SH-SY5Y cells. In addition, emodin inhibited the activation of the PI3K/mTOR/GSK3β signaling pathway. What is more, the PI3K/mTOR/GSK3β pathway participated in the protective mechanism of emodin on H2O2-induced cell damage. Collectively, it suggests that emodin alleviates H2O2-induced apoptosis and neuroinflammation potentially by regulating the PI3K/mTOR/GSK3β signaling pathway.

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SIRT1 activation inhibits hyperglycemia-induced apoptosis by reducing oxidative stress and mitochondrial dysfunction in human endothelial cells

Molecular Medicine Reports ◽

10.3892/mmr.2017.7027 ◽

2017 ◽

Vol 16 (3) ◽

pp. 3331-3338 ◽

Cited By ~ 17

Author(s):

Shengqiang Wang ◽

Jian Wang ◽

Airong Zhao ◽

Jigang Li

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Mitochondrial Dysfunction ◽

Human Endothelial Cells ◽

Induced Apoptosis

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Deltamethrin Induces Apoptosis in Cerebrum Neurons of Quail via Promoting Endoplasmic Reticulum Stress and Mitochondrial Dysfunction

10.21203/rs.3.rs-808891/v1 ◽

2021 ◽

Author(s):

Pengfei Wu ◽

Bing Han ◽

Qingyue Yang ◽

Siyu Li ◽

Xiaoqiao Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Endoplasmic Reticulum ◽

Er Stress ◽

Mitochondrial Dysfunction ◽

Chronic Exposure ◽

Molecular Mechanisms ◽

Atp Content ◽

Histological Changes ◽

Real Time Quantitative Pcr ◽

Induced Apoptosis

Abstract Deltamethrin (DLM) is a widely used and highly effective insecticide. DLM exposure is harmful to animal and human. Quail, as a bird model, has been widely used in the toxicology field. However, there is little information available in the literature about quail cerebrum damage caused by DLM. Here, we investigated the effect of DLM on quail cerebrum neurons. Four groups of healthy quails were assigned (10 quails in each group), respectively given 0, 15, 30, and 45 mg/kg DLM by gavage for 12 weeks. Through the measurements of quail cerebrum, it was found that DLM exposure induced obvious histological changes, oxidative stress, and neurons apoptosis. To further explore the possible molecular mechanisms, we performed real-time quantitative PCR to detect the expression of endoplasmic reticulum (ER) stress-related mRNA. In addition, we detected ATP content in quail cerebrum to evaluate the functional status of mitochondria. The study showed that DLM exposure significantly increased the expression of ER stress-related mRNA and decreased ATP content in quail cerebrum. These results suggest that chronic exposure to DLM induces apoptosis of quail cerebrum neurons via promoting ER stress and mitochondrial dysfunction. Furthermore, our results provide a novel explanation for DLM-induced apoptosis of avian cerebrum neurons.

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