scholarly journals Melatonin Represses Mitophagy to Protect Mouse Granulosa Cells from Oxidative Damage

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 968
Author(s):  
Yi Jiang ◽  
Ming Shen ◽  
Yuanyuan Chen ◽  
Yinghui Wei ◽  
Jingli Tao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Circadian Rhythms ◽  
Oxidative Damage ◽  
Cell Viability ◽  
Granulosa Cells ◽  
Therapeutic Target ◽  
Potential Therapeutic Target ◽  
Protective Mechanisms

Various environmental stimuli, including oxidative stress, could lead to granulosa cell (GC) death through mitophagy. Recently, it was reported that melatonin (MEL) has a significant effect on GC survival during oxidative damage. Here, we found that MEL inhibited oxidative stress-induced mitophagy to promote GC survival. The loss of cell viability upon H2O2 exposure was significantly restored after MEL treatment. Concomitantly, MEL inhibited the activation of mitophagy during oxidative stress. Notably, blocking mitophagy repressed GC death caused by oxidative stress. However, MEL cannot further restore viability of cells treated with mitophagy inhibitor. Moreover, PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine/threonine-protein kinase, was inhibited by MEL during oxidative stress. As a result, the E3 ligase Parkin failed to translocate to mitochondria, leading to impaired mitochondria clearance. Using RNAi to knock down PINK1 expression, we further verified the role of the MEL-PINK1-Parkin (MPP) pathway in maintaining GC survival by suppressing mitophagy. Our findings not only clarify the protective mechanisms of MEL against oxidative damage in GCs, but also extend the understanding about how circadian rhythms might influence follicles development in the ovary. These findings reveal a new mechanism of melatonin in defense against oxidative damage to GCs by repressing mitophagy, which may be a potential therapeutic target for anovulatory disorders.

Wild-type IDH2 protects nuclear DNA from oxidative damage and is a potential therapeutic target in colorectal cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Shuang Qiao ◽  
Wenhua Lu ◽  
Christophe Glorieux ◽  
Jiangjiang Li ◽  
Peiting Zeng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Oxidative Damage ◽  
Therapeutic Target ◽  
Nuclear Dna ◽  
Wild Type ◽  
Potential Therapeutic Target

T-LAK Cell-Originated Protein Kinase (TOPK) as a Prognostic Factor and a Potential Therapeutic Target in Ovarian Cancer

2016 ◽  
Vol 22 (24) ◽  
pp. 6110-6117 ◽  
Author(s):  
Yuji Ikeda ◽  
Jae-Hyun Park ◽  
Takashi Miyamoto ◽  
Naofumi Takamatsu ◽  
Taigo Kato ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Protein Kinase ◽  
Prognostic Factor ◽  
Therapeutic Target ◽  
Potential Therapeutic Target ◽  
Lak Cell

scholarly journals Effects of Caloric Restriction on Cardiac Oxidative Stress and Mitochondrial Bioenergetics: Potential Role of Cardiac Sirtuins

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ken Shinmura
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Oxidative Damage ◽  
Caloric Restriction ◽  
Functional Decline ◽  
Cellular Damage ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Stress Theory

The biology of aging has not been fully clarified, but the free radical theory of aging is one of the strongest aging theories proposed to date. The free radical theory has been expanded to the oxidative stress theory, in which mitochondria play a central role in the development of the aging process because of their critical roles in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function associated with the accumulation of oxidative damage might be responsible, at least in part, for the decline in cardiac performance with age. In contrast, lifelong caloric restriction can attenuate functional decline with age, delay the onset of morbidity, and extend lifespan in various species. The effect of caloric restriction appears to be related to a reduction in cellular damage induced by reactive oxygen species. There is increasing evidence that sirtuins play an essential role in the reduction of mitochondrial oxidative stress during caloric restriction. We speculate that cardiac sirtuins attenuate the accumulation of oxidative damage associated with age by modifying specific mitochondrial proteins posttranscriptionally. Therefore, the distinct role of each sirtuin in the heart subjected to caloric restriction should be clarified to translate sirtuin biology into clinical practice.

scholarly journals The Role of Cellular Prion Protein in Cancer Biology: A Potential Therapeutic Target

2021 ◽  
Vol 11 ◽  
Author(s):  
Manqiu Ding ◽  
Yongqiang Chen ◽  
Yue Lang ◽  
Li Cui
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Cell Survival ◽  
Cancer Cells ◽  
Prion Protein ◽  
Therapeutic Target ◽  
Cancer Biology ◽  
Cellular Prion Protein ◽  
Potential Therapeutic Target

Prion protein has two isoforms including cellular prion protein (PrPC) and scrapie prion protein (PrPSc). PrPSc is the pathological aggregated form of prion protein and it plays an important role in neurodegenerative diseases. PrPC is a glycosylphosphatidylinositol (GPI)-anchored protein that can attach to a membrane. Its expression begins at embryogenesis and reaches the highest level in adulthood. PrPC is expressed in the neurons of the nervous system as well as other peripheral organs. Studies in recent years have disclosed the involvement of PrPC in various aspects of cancer biology. In this review, we provide an overview of the current understanding of the roles of PrPC in proliferation, cell survival, invasion/metastasis, and stem cells of cancer cells, as well as its role as a potential therapeutic target.

scholarly journals SHP2 promotes NETosis through ERK5 pathway and mediates the development of psoriasis

2021 ◽  
Author(s):  
Yang Sun ◽  
Yan Ding ◽  
Jiao Qu ◽  
Chenyang Zhang ◽  
Yuyu Zhu ◽  
...  
Keyword(s):  
Immune Cells ◽  
Experimental Verification ◽  
Inflammatory Disease ◽  
Therapeutic Target ◽  
Tyrosine Phosphatase ◽  
Skin Lesions ◽  
Chronic Inflammatory Disease ◽  
Potential Therapeutic Target ◽  
Single Cell Rna Sequencing

Psoriasis is a chronic inflammatory disease which infiltrated a large number of neutrophils among skin lesions. Here, we investigated the contribution of tyrosine phosphatase SHP2 in neutrophils, as well as its pathogenesis in psoriasis. We combined single-cell RNA sequencing with experimental verification to declare that SHP2 in neutrophils could promote the NETs formation through the ERK5 pathway, and resulted in the infiltration of inflammatory immune cells, which leads to psoriasis. Our study provides evidence for the role of SHP2 in NETosis in the progression of psoriasis, and SHP2 may be a potential therapeutic target for the treatment of psoriasis.

scholarly journals Time-of-day-dependent responses of cyanobacterial cellular viability against oxidative stress

2019 ◽  
Author(s):  
Kenya Tanaka ◽  
Ginga Shimakawa ◽  
Shuji Nakanishi
Keyword(s):  
Oxidative Stress ◽  
Circadian Rhythms ◽  
Cell Viability ◽  
Circadian Clock ◽  
Stress Tolerance ◽  
Time Of Day ◽  
Circadian Oscillation ◽  
Subjective Time ◽  
Rhythmic Pattern ◽  
Oxidative Stress Tolerance

AbstractAs an adaptation to periodic fluctuations of environmental light, photosynthetic organisms have evolved a circadian clock. Control by the circadian clock of many cellular physiological functions, including antioxidant enzymes, metabolism and the cell cycle, has attracted attention in the context of oxidative stress tolerance. However, since each physiological function works in an integrated manner to deal with oxidative stress, whether or not cell responses to oxidative stress are under circadian control remains an open question. In fact, circadian rhythms of oxidative stress tolerance have not yet been experimentally demonstrated. In the present work, we applied an assay using methyl viologen (MV), which generates reactive oxygen species (ROS) under light irradiation, and experimentally verified the circadian rhythms of oxidative stress tolerance in photosynthetic cells of the cyanobacterium Synechococcus elongatus PCC7942, a standard model species for investigation of the circadian clock. Here, we report that ROS generated by MV treatment causes damage to stroma components and not to the photosynthetic electron transportation chain, leading to reduced cell viability. The degree of decrease in cell viability was dependent on the subjective time at which oxidative stress was applied. Thus, oxidative stress tolerance was shown to exhibit circadian rhythms. In addition, the rhythmic pattern of oxidative stress tolerance disappeared in mutant cells lacking the essential clock genes. Notably, ROS levels changed periodically, independent of the MV treatment. Thus, we demonstrate for the first time that in cyanobacterial cells, oxidative stress tolerance shows circadian oscillation.

scholarly journals Protective Effect of L-carnitine on the Oxidative Stress Injury of Human Ovarian Granulosa Cells

2021 ◽  
Author(s):  
Xuening Li ◽  
Xiaodong Wu ◽  
Yuemin Zhang ◽  
Tianyi Ma ◽  
Pingping Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Cell Viability ◽  
Granulosa Cells ◽  
Blank Group ◽  
Stress Injury ◽  
Ovarian Granulosa Cells ◽  
Nuclear Pyknosis ◽  
Mda Content

Abstract The protective effect of L-carnitine (LC) on the oxidative stress (OS) injury and the effect of L-carnitine on follicular stimulating hormone receptor (FSHR) of ovarian granulosa cells (GCs) were investigated. OS was induced by treatment with H2O2. We cultured KGN cells in four groups: the blank group, OS group and two L-carnitine pretreatment group (low, high). In the OS group, cell nuclear pyknosis was observed, mitochondria swelled irregularly and their cristae were fractured. Meanwhile, the cell viability, superoxide dismutase (SOD) and glutathione (GSH) contents, mitochondrial membrane potential (ΔΨm) and the level of FSHR expression were significantly decreased in the OS group. However, malonaldehyde (MDA) content, reactive oxygen species (ROS) level and apoptosis rate were significantly increased. Compared with the OS group, the morphology of cells and mitochondria in the L-carnitine pretreatment group were improved, the cell viability and the expression of FSHR was significantly increased, and the OS level was decreased. These results indicated that L-carnitine can protect the cells from OS damage induced by H2O2, enhance the antioxidant and anti-apoptotic ability of GCs, and alleviate the decrease of FSHR expression on GCs caused by OS. Therefore, L-carnitine may help prevent the ovarian aging and improve the quality of follicles.

Sign in / Sign up

Export Citation Format

Share Document