scholarly journals Arabidopsis APx-R Is a Plastidial Ascorbate-Independent Peroxidase Regulated by Photomorphogenesis

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 65
Author(s):  
Fernanda Lazzarotto ◽  
Khadija Wahni ◽  
Maiara Piovesana ◽  
Felipe Maraschin ◽  
Joris Messens ◽  
...  
Keyword(s):  
Ascorbate Peroxidase ◽  
Cell Injury ◽  
Small Subset ◽  
Oxygen Species ◽  
Loss Of Function ◽  
Direct Role ◽  
Antioxidant Metabolism ◽  
Heme Peroxidase ◽  
Constitutive Overexpression

Peroxidases are enzymes that catalyze the reduction of hydrogen peroxide, thus minimizing cell injury and modulating signaling pathways as response to this reactive oxygen species. Using a phylogenetic approach, we previously identified a new peroxidase family composed of a small subset of ascorbate peroxidase (APx) homologs with distinguished features, which we named ascorbate peroxidase-related (APx-R). In this study, we showed that APx-R is an ascorbate-independent heme peroxidase. Despite being annotated as a cytosolic protein in public databases, transient expression of AtAPx-R-YFP in Arabidopsis thaliana protoplasts and stable overexpression in plants showed that the protein is targeted to plastids. To characterize APx-R participation in the antioxidant metabolism, we analyzed loss-of-function mutants and AtAPx-R overexpressing lines. Molecular analysis showed that glutathione peroxidase 7 (GPx07) is specifically induced to compensate the absence of APx-R. APx-R overexpressing lines display faster germination rates, further confirming the involvement of APx-R in seed germination. The constitutive overexpression of AtAPx-R-YFP unraveled the existence of a post-translational mechanism that eliminates APx-R from most tissues, in a process coordinated with photomorphogenesis. Our results show a direct role of APx-R during germinative and post-germinative development associated with etioplasts differentiation.

scholarly journals CircHIPK3 regulates the autophagy and apoptosis of hypoxia/reoxygenation-stimulated cardiomyocytes via the miR-20b-5p/ATG7 axis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zhimei Qiu ◽  
Yan Wang ◽  
Weiwei Liu ◽  
Chaofu Li ◽  
Ranzun Zhao ◽  
...  
Keyword(s):  
Cell Injury ◽  
Ischemia Reperfusion ◽  
Circular Rna ◽  
Control Group ◽  
Loss Of Function ◽  
Cardiomyocyte Autophagy ◽  
Myocardial Ischemia Reperfusion ◽  
Injury Research ◽  
Hypoxia Reoxygenation

AbstractAutophagy and apoptosis are involved in myocardial ischemia/reperfusion (I/R) injury. Research indicates that circular RNA HIPK3 (circHIPK3) is crucial to cell autophagy and apoptosis in various cancer types. However, the role of circHIPK3 in the regulation of cardiomyocyte autophagy and apoptosis during I/R remains unknown. Our study aimed to examine the regulatory effect of circHIPK3 during myocardial I/R and investigate its mechanism in cardiomyocyte autophagy and apoptosis. Methods and results. The expression of circHIPK3 was upregulated during myocardial I/R injury and hypoxia/reoxygenation (H/R) injury of cardiomyocytes. To study the potential role of circHIPK3 in myocardial H/R injury, we performed gain-of-function and loss-of-function analyses of circHIPK3 in cardiomyocytes. Overexpression of circHIPK3 significantly promoted H/R-induced cardiomyocyte autophagy and cell injury (increased intracellular reactive oxygen species (ROS) and apoptosis) compared to those in the control group, while silencing of circHIPK3 showed the opposite effect. Further research found that circHIPK3 acted as an endogenous miR-20b-5p sponge to sequester and inhibit miR-20b-5p activity, resulting in increased ATG7 expression. In addition, miR-20b-5p inhibitors reversed the decrease in ATG7 induced by silencing circHIPK3. Conclusions. CircHIPK3 can accelerate cardiomyocyte autophagy and apoptosis during myocardial I/R injury through the miR-20b-5p/ATG7 axis. These data suggest that circHIPK3 may serve as a potential therapeutic target for I/R.

Coordinated Action of miR-146a and Parkin Gene Regulate Rotenone-induced Neurodegeneration

2020 ◽  
Vol 176 (2) ◽  
pp. 433-445 ◽  
Author(s):  
Abhishek Jauhari ◽  
Tanisha Singh ◽  
Saumya Mishra ◽  
Jai Shankar ◽  
Sanjay Yadav
Keyword(s):  
Reactive Oxygen Species ◽  
Promoter Region ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Parkin Gene ◽  
Direct Role ◽  
Common Cause ◽  
Nuclear Factor Kappa Beta ◽  
Rotenone Exposure

Abstract Mitochondrial dysfunction is a common cause in pathophysiology of different neurodegenerative diseases. Elimination of dysfunctional and damaged mitochondria is a key requirement for maintaining homeostasis and bioenergetics of degenerating neurons. Using global microRNA (miRNA) profiling in a systemic rotenone model of Parkinson’s disease, we have identified miR-146a as upmost-regulated miRNA, which is known as inflammation regulatory miRNA. Here, we report the role of activated nuclear factor kappa beta (NF-kβ) in miR-146a-mediated downregulation of Parkin protein, which inhibits clearance of damaged mitochondria and induces neurodegeneration. Our studies have shown that 4-week rotenone exposure (2.5 mg/kg b.wt) induced oxidative imbalance-mediated NF-kβ activation in 1-year-old rat’s brain. Activated NF-kβ binds in promoter region of miR-146a gene and induces its transcription, which downregulates levels of Parkin protein. Decreased amount of Parkin protein results in accumulation of damaged and dysfunctional mitochondria, which further promotes the generation of reactive oxygen species in degenerating neurons. In conclusion, our studies have identified direct role of NF-kβ-mediated upregulation of miR-146a in regulating mitophagy through inhibition of the Parkin gene.

scholarly journals Melatonin reduces oxidative damage in mouse granulosa cells via restraining JNK-dependent autophagy

Reproduction ◽  
2018 ◽  
Vol 155 (3) ◽  
pp. 307-319 ◽  
Author(s):  
Yan Cao ◽  
Ming Shen ◽  
Yi Jiang ◽  
Shao-chen Sun ◽  
Honglin Liu
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Mammalian Cells ◽  
Therapeutic Strategies ◽  
Oxygen Species ◽  
Protective Effects ◽  
Follicular Atresia ◽  
Direct Role ◽  
Jnk Pathway

Oxidative stress-induced granulosa cell (GCs) injury is believed to be a common trigger for follicular atresia. Emerging evidence indicates that excessive autophagy occurs in mammalian cells with oxidative damage. N-acetyl-5-methoxytrypamine (melatonin) has been shown to prevent GCs from oxidative injury, although the exact mechanism remains to be elucidated. Here, we first demonstrated that the suppression of autophagy through the JNK/BCL-2/BECN1 signaling is engaged in melatonin-mediated GCs protection against oxidative damage. Melatonin inhibited the loss of GCs viability, formation of GFP-MAP1LC3B puncta, accumulation of MAP1LC3B-II blots, degradation of SQSTM1 and the expression of BECN1, which was correlated with impaired activation of JNK during oxidative stress. On the other hand, blocking of autophagy and/or JNK also reduced the level of H2O2-induced GCs death, but failed to further restore GCs viability in the presence of melatonin. Particularly, the suppression of autophagy provided no additional protective effects when GCs were pretreated with JNK inhibitor and/or melatonin. Importantly, we found that the enhanced interaction between BCL-2 and BECN1 might be a responsive mechanism for autophagy suppression via the melatonin/JNK pathway. Moreover, blocking the downstream antioxidant system of melatonin using specific inhibitors further confirmed a direct role of melatonin/JNK/autophagy axis in preserving GCs survival without scavenging reactive oxygen species (ROS). Taken together, our findings uncover a novel function of melatonin in preventing GCs from oxidative damage by targeting JNK-mediated autophagy, which might contribute to develop therapeutic strategies for patients with ovulation failure-related disorders.

scholarly journals Inhibition of granulocyte ROS production by opioids prevents regeneration

2017 ◽  
Author(s):  
Elodie Labit ◽  
Lise Rabiller ◽  
Christophe Guissard ◽  
Mireille Andre ◽  
Christine Rampon ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Gold Standard ◽  
Tissue Repair ◽  
Opioid Antagonist ◽  
Ros Production ◽  
Oxygen Species ◽  
Loss Of Function ◽  
Adult Zebrafish ◽  
Mu Receptors

SUMMARYInhibition of regeneration and induction of healing are classic outcomes of tissue repair in adult mammals. Here, by using gain and loss of function experiments, we demonstrate that both endogenous and exogenous opioids prevent tissue regeneration in adults, by inhibiting the early reactive oxygen species (ROS) production occurring after lesion and required for regeneration. These effects can be overcome and regeneration induced by the use of an opioid antagonist. These results, obtained in both gold-standard adult zebrafish and a newly-developed model of regeneration in adult mammals, demonstrate that this mechanism can be considered as a general paradigm in vertebrates. In addition, we show that opioids act via signaling through peripheral mu-receptors expressed on granulocytes. This work clearly demonstrates the deleterious role of opioids on tissue regeneration through the control of ROS production in vertebrates and thus questions about opioid-based analgesia in perioperative care.

Prostanoid release by Kupffer cells upon hypoxia-reoxygenation: role of pHi and Cai2+

1993 ◽  
Vol 264 (3) ◽  
pp. G535-G540 ◽  
Author(s):  
M. Gyenes ◽  
H. De Groot
Keyword(s):  
Kupffer Cells ◽  
Cell Injury ◽  
Primary Cultures ◽  
Maximum Level ◽  
Leukotriene B4 ◽  
Oxygen Species ◽  
Thromboxane Production ◽  
Prostanoid Synthesis ◽  
Hypoxia Reoxygenation

Primary cultures of rat Kupffer cells liberated significant amounts of prostaglandin (PG) D2, PGE2, and thromboxane (measured as thromboxane B2) when exposed to reoxygenation after 4 h of hypoxia. After a delayed onset, prostanoids were released at high rates for at least 8 h and after that time 700 pmol PGD2, 280 pmol PGE2, and 200 pmol thromboxane per 10(6) cells had been liberated. Unlike prostanoid release, leukotriene B4 production in reoxygenated cell cultures was only twice as much as in aerobic controls. Superoxide dismutase and catalase had no effect on PGD2, PGE2, and thromboxane production, indicating that prostanoid formation was independent of reactive oxygen species generated extracellularly and of cell injury. On the other hand, diphenyliodonium, as well as amiloride, blocked hypoxia-reoxygenation-induced PGD2, PGE2, and thromboxane release. The elevated prostanoid synthesis was preceded by increases in intracellular pH (from 7.23 to 7.38) and in intracellular Ca2+ (from 55 nM to a maximum level of 807 nM). These observations suggest a participation of NADPH oxidase and a related Na(+)-H+ exchange in the enhanced prostanoid synthesis, probably through the induction of an increased intracellular Ca2+ concentration.

scholarly journals BKCa (Slo) Channel Regulates Mitochondrial Function and Lifespan in Drosophila melanogaster

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 945 ◽  
Author(s):  
Shubha Gururaja Rao ◽  
Piotr Bednarczyk ◽  
Atif Towheed ◽  
Kajol Shah ◽  
Priyanka Karekar ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Mitochondrial Function ◽  
Physiological Role ◽  
Oxygen Species ◽  
Organ Protection ◽  
Bkca Channels ◽  
Direct Role ◽  
Mitochondrial Structure ◽  
And Function

BKCa channels, originally discovered in Drosophila melanogaster as slowpoke (slo), are recognized for their roles in cellular and organ physiology. Pharmacological approaches implicated BKCa channels in cellular and organ protection possibly for their ability to modulate mitochondrial function. However, the direct role of BKCa channels in regulating mitochondrial structure and function is not deciphered. Here, we demonstrate that BKCa channels are present in fly mitochondria, and slo mutants show structural and functional defects in mitochondria. slo mutants display an increase in reactive oxygen species and the modulation of ROS affected their survival. We also found that the absence of BKCa channels reduced the lifespan of Drosophila, and overexpression of human BKCa channels in flies extends life span in males. Our study establishes the presence of BKCa channels in mitochondria of Drosophila and ascertains its novel physiological role in regulating mitochondrial structural and functional integrity, and lifespan.

Upregulation of Id-1 via BMP-2 receptors induces reactive oxygen species in podocytes

2006 ◽  
Vol 291 (3) ◽  
pp. F654-F662 ◽  
Author(s):  
Gregor Pache ◽  
Christina Schäfer ◽  
Sebastian Wiesemann ◽  
Erik Springer ◽  
Max Liebau ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Line ◽  
Kidney Development ◽  
Cell Injury ◽  
Reactive Oxygen ◽  
Cancer Cell Line ◽  
Negative Regulator ◽  
Oxygen Species ◽  
Bmp Receptors

Bone morphogenetic proteins (BMPs) are secreted signaling molecules, which play a major role in kidney development and disease. Here, we show the existence of mRNA for BMP-2 and for the BMP receptors BMPR1A, BMPR1B, BMPRII, ACVR1A, ACVR2, and ACVR2B in differentiated mouse podocytes and the protein expression of BMPR1A in human glomerular podocytes. BMP-2 dose dependently increases the free cytosolic Ca2+ concentration in podocytes proving the existence of a functional receptor in these cells. Recent data indicate that in a myoblastic cell line and in a breast cancer cell line, BMP-2 increases the expression of Id-1, a negative regulator of basic helix-loop-helix transcription factors, but the role of BMP-2 stimulated Id-1 expression in the kidney has not been further characterized. Here, we show that BMP-2 increases the expression of Id-1 in differentiated podocytes. To investigate a role of Id-1 for podocyte function, overexpression of Id-1 was induced in differentiated mouse podocytes. Id-1-overexpressing podocytes show an increased NADPH-dependent production of reactive oxygen species (ROS). This effect can be evoked by BMP-2 and can be antagonized by anti-Id-1 antisense oligonucleotides. The data indicate that BMP-2 may, via an increased expression of Id-1 and an increased generation of ROS, contribute to important cellular functions in podocytes. ROS supposedly play a major role in cell adhesion, cell injury, ion transport, fibrogenesis, angiogenesis and are involved in the pathogenesis of membranous nephropathy.

scholarly journals Overexpression of FTO Protects Human Granulosa Cells From Cisplatin-Induced Injury

2021 ◽  
Author(s):  
Rongli Wang ◽  
Xinyuan Yang
Keyword(s):  
Stem Cells ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Cell Injury ◽  
Ovarian Failure ◽  
Regulation Mechanism ◽  
Loss Of Function ◽  
Young Females ◽  
Rna Transfection

Abstract Background: Premature ovarian failure (POF) is a serious problem for young women who received chemotherapy, and its pathophysiological basis is the dysfunction of granulosa cells. The RNA methylation on the sixth Natom of adenylate (m6A) plays an important role in epigenetic regulation, and previous studies have demonstrated that the fat mass- and obesity-associated (FTO) was decreased in POF and may be a biomarker for the occurrence of POF. Furthermore, to preserve the fertility of these young females, various approaches have been used to prevent chemotherapy-induced ovarian failure, and menstrual-derived stem cells (MenSCs) have been considered as a promising treatment strategy. Here, we aimed to explore the role of FTO in the MenSCs recovering the function of injured granulosa cells.Method: First, the cisplatin was used to make a granulosa cell injury model. Then, the menstrual-derived stem cells (MenSCs)-injured granulosa cells co-culture model and POF mouse model were established in this study to explore the role of FTO. Human ovarian granulosa cell lines (KGN) were used to explore the effect of FTO on cell proliferation and apoptosis. Furthermore, gain- and loss-of-function studies, small interfering RNA transfection, and meclofenamic acid (MA), a highly selective inhibitor of FTO, were also conducted to clarified the regulation mechanism of FTO in granulosa.Results: MenSCs co-culture could improve the function of injured granulosa cells by increasing the expression of FTO. MenSCs transplantation could restore the expression of FTO in the ovary of POF mice. Overexpression of FTO could restore the injured cells’ proliferation and decrease its apoptosis through regulating the expression of BNIP3. Down-regulation of FTO got the opposite results.Conclusion: FTO has a protective effect, which could improve the viability of granulosa cells after cisplatin treatment by decreasing the expression of BNIP3, and it may provide new insight into the therapeutic targets for the cisplatin-induced POF.

E3 ubiquitin ligases

2005 ◽  
Vol 41 ◽  
pp. 15-30 ◽  
Author(s):  
Helen C. Ardley ◽  
Philip A. Robinson
Keyword(s):  
Protein Complexes ◽  
Loss Of Function ◽  
Direct Role ◽  
Cellular Processes ◽  
Substrate Protein ◽  
Protein Ubiquitination ◽  
C Terminus ◽  
Full Complement ◽  
Spatio Temporal ◽  
Eukaryotic Organisms

The selectivity of the ubiquitin–26 S proteasome system (UPS) for a particular substrate protein relies on the interaction between a ubiquitin-conjugating enzyme (E2, of which a cell contains relatively few) and a ubiquitin–protein ligase (E3, of which there are possibly hundreds). Post-translational modifications of the protein substrate, such as phosphorylation or hydroxylation, are often required prior to its selection. In this way, the precise spatio-temporal targeting and degradation of a given substrate can be achieved. The E3s are a large, diverse group of proteins, characterized by one of several defining motifs. These include a HECT (homologous to E6-associated protein C-terminus), RING (really interesting new gene) or U-box (a modified RING motif without the full complement of Zn2+-binding ligands) domain. Whereas HECT E3s have a direct role in catalysis during ubiquitination, RING and U-box E3s facilitate protein ubiquitination. These latter two E3 types act as adaptor-like molecules. They bring an E2 and a substrate into sufficiently close proximity to promote the substrate's ubiquitination. Although many RING-type E3s, such as MDM2 (murine double minute clone 2 oncoprotein) and c-Cbl, can apparently act alone, others are found as components of much larger multi-protein complexes, such as the anaphase-promoting complex. Taken together, these multifaceted properties and interactions enable E3s to provide a powerful, and specific, mechanism for protein clearance within all cells of eukaryotic organisms. The importance of E3s is highlighted by the number of normal cellular processes they regulate, and the number of diseases associated with their loss of function or inappropriate targeting.

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