scholarly journals Irisin alleviates obesity-related spermatogenesis dysfunction via the regulation of the AMPKα signalling pathway

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yang Mu ◽  
Huang-Guan Dai ◽  
Ling-Bo Luo ◽  
Jing Yang
Keyword(s):  
Oxidative Stress ◽  
Sperm Count ◽  
Underlying Mechanism ◽  
Signalling Pathway ◽  
Protective Effects ◽  
Exercise Induced ◽  
Amp Activated Protein Kinase

Abstract Background Infertility is a common complication in obese men. Oxidative stress and testicular apoptosis play critical roles in obesity-induced spermatogenesis dysfunction. It has been reported that irisin, an exercise-induced myokine, may attenuate oxidative damage and testicular apoptosis in several diseases; however, its role in obesity-induced spermatogenesis dysfunction remains unclear. The purpose of this study was to investigate the role and underlying mechanism of irisin in obesity-induced dysfunction of spermatogenesis. Methods Male mice were fed a high-fat diet (HFD) for 24 weeks to establish a model of obesity-induced spermatogenesis dysfunction. To explore the effects of irisin, mice were subcutaneously infused with recombinant irisin for 8 weeks beginning at 16 weeks after starting a HFD. To confirm the role of AMP-activated protein kinase α (AMPKα), AMPKα-deficient mice were used. Results The data showed decreased serum irisin levels in obese patients, which was negatively correlated with sperm count and progressive motility. Irisin was downregulated in the plasma and testes of obese mice. Supplementation with irisin protected against HFD-induced spermatogenesis dysfunction and increased testosterone levels in mice. HFD-induced oxidative stress, endoplasmic reticulum (ER) stress and testicular apoptosis were largely attenuated by irisin treatment. Mechanistically, we identified that irisin activated the AMPKα signalling pathway. With AMPKα depletion, we found that the protective effects of irisin on spermatogenesis dysfunction were abolished in vivo and in vitro. Conclusions In conclusion, we found that irisin alleviated obesity-related spermatogenesis dysfunction via activation of the AMPKα signalling pathway. Based on these findings, we hypothesized that irisin is a potential therapeutic agent against obesity-related spermatogenesis dysfunction.

scholarly journals Protection against Doxorubicin-Induced Cytotoxicity by Geniposide Involves AMPKα Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yan-Yan Meng ◽  
Yu-Pei Yuan ◽  
Xin Zhang ◽  
Chun-Yan Kong ◽  
Peng Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Potential ◽  
Cell Loss ◽  
Protective Role ◽  
Protective Effects ◽  
Morphological Examination ◽  
Heart Injury ◽  
Amp Activated Protein Kinase

Oxidative stress and cardiomyocyte apoptosis play critical roles in the development of doxorubicin- (DOX-) induced cardiotoxicity. Our previous study found that geniposide (GE) could inhibit cardiac oxidative stress and apoptosis of cardiomyocytes but its role in DOX-induced heart injury remains unknown. Our study is aimed at investigating whether GE could protect against DOX-induced heart injury. The mice were subjected to a single intraperitoneal injection of DOX (15 mg/kg) to induce cardiomyopathy model. To explore the protective effects, GE was orally given for 10 days. The morphological examination and biochemical analysis were used to evaluate the effects of GE. H9C2 cells were used to verify the protective role of GE in vitro. GE treatment alleviated heart dysfunction and attenuated cardiac oxidative stress and cell loss induced by DOX in vivo and in vitro. GE could activate AMP-activated protein kinase α (AMPKα) in vivo and in vitro. Moreover, inhibition of AMPKα could abolish the protective effects of GE against DOX-induced oxidative stress and apoptosis. GE could protect against DOX-induced heart injury via activation of AMPKα. GE has therapeutic potential for the treatment of DOX cardiotoxicity.

scholarly journals Protective Effects of Dietary Antioxidants against Vanadium-Induced Toxicity: A Review

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Iwona Zwolak
Keyword(s):  
Oxidative Stress ◽  
Animal Studies ◽  
Toxic Metal ◽  
Protective Effects ◽  
Dietary Antioxidants ◽  
Vanadium Toxicity ◽  
Preventive Effects

Vanadium (V) in its inorganic forms is a toxic metal and a potent environmental and occupational pollutant and has been reported to induce toxic effects in animals and people. In vivo and in vitro data show that high levels of reactive oxygen species are often implicated in vanadium deleterious effects. Since many dietary (exogenous) antioxidants are known to upregulate the intrinsic antioxidant system and ameliorate oxidative stress-related disorders, this review evaluates their effectiveness in the treatment of vanadium-induced toxicity. Collected data, mostly from animal studies, suggest that dietary antioxidants including ascorbic acid, vitamin E, polyphenols, phytosterols, and extracts from medicinal plants can bring a beneficial effect in vanadium toxicity. These findings show potential preventive effects of dietary antioxidants on vanadium-induced oxidative stress, DNA damage, neurotoxicity, testicular toxicity, and kidney damage. The relevant mechanistic insights of these events are discussed. In summary, the results of studies on the role of dietary antioxidants in vanadium toxicology appear encouraging enough to merit further investigations.

scholarly journals MiR-22 Inhibition Alleviates Cardiac Dysfunction in Doxorubicin-Induced Cardiomyopathy by Targeting the sirt1/PGC-1α Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Runze Wang ◽  
Yuerong Xu ◽  
Xiaolin Niu ◽  
Yexian Fang ◽  
Dong Guo ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Poor Prognosis ◽  
Cardiac Fibrosis ◽  
Underlying Mechanism ◽  
Protective Effects ◽  
Loss Of Function ◽  
Life Threatening

Doxorubicin (DOX) cardiotoxicity is a life-threatening side effect that leads to a poor prognosis in patients receiving chemotherapy. We investigated the role of miR-22 in doxorubicin-induced cardiomyopathy and the underlying mechanism in vivo and in vitro. Specifically, we designed loss-of-function and gain-of-function experiments to identify the role of miR-22 in doxorubicin-induced cardiomyopathy. Our data suggested that inhibiting miR-22 alleviated cardiac fibrosis and cardiac dysfunction induced by doxorubicin. In addition, inhibiting miR-22 mitigated mitochondrial dysfunction through the sirt1/PGC-1α pathway. Knocking out miR-22 enhanced mitochondrial biogenesis, as evidenced by increased PGC-1α, TFAM, and NRF-1 expression in vivo. Furthermore, knocking out miR-22 rescued mitophagy, which was confirmed by increased expression of PINK1 and parkin and by the colocalization of LC3 and mitochondria. These protective effects were abolished by overexpressing miR-22. In conclusion, miR-22 may represent a new target to alleviate cardiac dysfunction in doxorubicin-induced cardiomyopathy and improve prognosis in patients receiving chemotherapy.

scholarly journals OsnR is an autoregulatory negative transcription factor controlling redox-dependent stress responses in Corynebacterium glutamicum

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Haeri Jeong ◽  
Younhee Kim ◽  
Heung-Shick Lee
Keyword(s):  
Oxidative Stress ◽  
Corynebacterium Glutamicum ◽  
Stress Responses ◽  
Promoter Region ◽  
Underlying Mechanism ◽  
In Vitro Assays ◽  
Expression Of Genes

Abstract Background Corynebacterium glutamicum is used in the industrial production of amino acids and nucleotides. During the course of fermentation, C. glutamicum cells face various stresses and employ multiple regulatory genes to cope with the oxidative stress. The osnR gene plays a negative regulatory role in redox-dependent oxidative-stress responses, but the underlying mechanism is not known yet. Results Overexpression of the osnR gene in C. glutamicum affected the expression of genes involved in the mycothiol metabolism. ChIP-seq analysis revealed that OsnR binds to the promoter region of multiple genes, including osnR and cg0026, which seems to function in the membrane-associated redox metabolism. Studies on the role of the osnR gene involving in vitro assays employing purified OsnR proteins and in vivo physiological analyses have identified that OsnR inhibits the transcription of its own gene. Further, oxidant diamide stimulates OsnR-binding to the promoter region of the osnR gene. The genes affected by the overexpression of osnR have been found to be under the control of σH. In the osnR-overexpressing strain, the transcription of sigH is significantly decreased and the stimulation of sigH transcription by external stress is lost, suggesting that osnR and sigH form an intimate regulatory network. Conclusions Our study suggests that OsnR not only functions as a transcriptional repressor of its own gene and of those involved in redox-dependent stress responses but also participates in the global transcriptional regulation by controlling the transcription of other master regulators, such as sigH.

Cytoglobin, a novel globin, plays an antifibrotic role in the kidney

2010 ◽  
Vol 299 (5) ◽  
pp. F1120-F1133 ◽  
Author(s):  
Imari Mimura ◽  
Masaomi Nangaku ◽  
Hiroshi Nishi ◽  
Reiko Inagi ◽  
Tetsuhiro Tanaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Kidney ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Protective Effects ◽  
Transgenic Rats ◽  
Cultured Fibroblasts

Cytoglobin (Cygb), a novel member of the globin superfamily, is expressed by fibroblasts in various organs. However, its function remains unknown. Because of its localization, we speculated that a biological role of Cygb may be related to fibrogenesis. To clarify the role of Cygb in kidney fibrosis, we employed the remnant kidney model in rats. Immunohistochemical analysis showed an increase in Cygb expression in parallel with disease progression. To investigate the functional consequence of Cygb upregulation, we established transgenic rats overexpressing rat Cygb. Overexpression of Cygb improved histological injury, preserved renal function, and ameliorated fibrosis, as estimated by the accumulation of collagen I and IV as well as Masson trichrome staining. These protective effects of Cygb were associated with a decrease in nitrotyrosine deposition in the kidney and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) excretion as a marker of oxidative stress. We also performed in vitro studies utilizing a rat kidney fibroblast cell line transiently overexpressing Cygb, an inducible kidney cell transfected with Cygb, and primary cultured fibroblasts isolated from the kidneys of the transgenic rats. These different experimental systems consistently showed that Cygb inhibited collagen synthesis. Furthermore, mutant disruption of heme in Cygb that impaired its antioxidant properties led to the loss of antifibrotic effects, suggesting that Cygb reduces fibrosis via a radical scavenging function. In conclusion, we showed that Cygb plays an important role in protection of the kidney against fibrosis via the amelioration of oxidative stress both in vitro and in vivo. Cygb might represent a good therapeutic target in chronic kidney disease.

Anti-fatigue effect of Lepidium meyenii Walp. (Maca) on preventing mitochondria-mediated muscle damage and oxidative stress in vivo and vitro

2021 ◽  
Vol 12 (7) ◽  
pp. 3132-3141
Author(s):  
Hongkang Zhu ◽  
Wenqian Xu ◽  
Ning Wang ◽  
Wenhao Jiang ◽  
Yuliang Cheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Muscle Damage ◽  
Aqueous Extract ◽  
Fatigue Effect ◽  
Lepidium Meyenii ◽  
Exercise Induced ◽  
And Oxidative Stress

We investigated the role of Maca aqueous extract on muscle during exercise-induced fatigue both in vivo and in vitro..

MiR-22-3p Suppresses Vascular Remodeling and Oxidative Stress by Targeting CHD9 during the Development of Hypertension

2021 ◽  
pp. 1-11
Author(s):  
Hanqing Chen ◽  
Xiru Xu ◽  
Zhengqing Liu ◽  
Yong Wu
Keyword(s):  
Oxidative Stress ◽  
Vascular Remodeling ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Spontaneously Hypertensive ◽  
Aortic Smooth Muscle ◽  
Phenotype Switch ◽  
And Oxidative Stress

Hypertension is considered a risk factor for a series of systematic diseases. Known factors including genetic predisposition, age, and diet habits are strongly associated with the initiation of hypertension. The current study aimed to investigate the role of miR-22-3p in hypertension. In this study, we discovered that the miR-22-3p level was significantly decreased in the thoracic aortic vascular tissues and aortic smooth muscle cells (ASMCs) of spontaneously hypertensive rats. Functionally, the overexpression of miR-22-3p facilitated the switch of ASMCs from the synthetic to contractile phenotype. To investigate the underlying mechanism, we predicted 11 potential target mRNAs for miR-22-3p. After screening, chromodomain helicase DNA-binding 9 (CHD9) was validated to bind with miR-22-3p. Rescue assays showed that the co-overexpression of miR-22-3p and CHD9 reversed the inhibitory effect of miR-22-3p mimics on cell proliferation, migration, and oxidative stress in ASMCs. Finally, miR-22-3p suppressed vascular remodeling and oxidative stress in vivo. Overall, miR-22-3p regulated ASMC phenotype switch by targeting CHD9. This new discovery provides a potential insight into hypertension treatment.

scholarly journals Oxidative stress promotes liver cancer metastasis via a PKA-activated RNF25/ECAD/YAP circuit

2022 ◽  
Author(s):  
Zhao Huang ◽  
Li Zhou ◽  
Jiufei Duan ◽  
Siyuan Qin ◽  
Yu Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cancer Metastasis ◽  
Anoikis Resistance ◽  
Antioxidant Genes ◽  
Redox Sensor ◽  
Stress Signals ◽  
Hcc Cells

Abstract Loss of E-cadherin (ECAD), often caused by epigenetic inactivation, is closely associated with tumor metastasis. However, how ECAD is regulated in response to oxidative stress during tumorigenesis is largely unknown. Here we identify RNF25 as a new E3 ligase of ECAD, whose activation by oxidative stress leads to ECAD protein degradation in hepatocellular carcinoma (HCC). Loss of ECAD activates YAP, which in turn promotes the transcription of RNF25, thus forming a positive feedback loop to sustain the ECAD downregulation. YAP activation mitigates oxidative stress in detached HCC cells by upregulating antioxidant genes, protecting detached HCC cells from ferroptosis, resulting in anoikis resistance. Mechanistically, we found that protein kinase A (PKA) senses oxidative stress by redox modification in its β catalytic subunit (PRKACB) at Cys200 and Cys344, which increases its kinase activity towards RNF25 phosphorylation at Ser450, facilitating RNF25-mediated degradation of ECAD. Moreover, RNF25 expression is associated with HCC metastasis and depletion of RNF25 is sufficient to diminish HCC invasion and metastasis in vitro and in vivo. Together, these results identify a dual role of RNF25 as a critical regulator of ECAD protein turnover, promoting both anoikis resistance and metastasis, and PKA is a necessary redox sensor to enable this process. Our study provides mechanistic insight into how tumor cells sense oxidative stress signals to spread while escaping cell death.

scholarly journals Tetrahydrocurcumin Ameliorates Diabetic Cardiomyopathy by Attenuating High Glucose-Induced Oxidative Stress and Fibrosis via Activating the SIRT1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Kaifeng Li ◽  
Mengen Zhai ◽  
Liqing Jiang ◽  
Fan Song ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Therapeutic Potential ◽  
Ros Generation ◽  
Protective Effects ◽  
Collagen Iii

Hyperglycemia-induced oxidative stress and fibrosis play a crucial role in the development of diabetic cardiomyopathy (DCM). Tetrahydrocurcumin (THC), a major bioactive metabolite of natural antioxidant curcumin, is reported to exert even more effective antioxidative and superior antifibrotic properties as well as anti-inflammatory and antidiabetic abilities. This study was designed to investigate the potential protective effects of THC on experimental DCM and its underlying mechanisms, pointing to the role of high glucose-induced oxidative stress and interrelated fibrosis. In STZ-induced diabetic mice, oral administration of THC (120 mg/kg/d) for 12 weeks significantly improved the cardiac function and ameliorated myocardial fibrosis and cardiac hypertrophy, accompanied by reduced reactive oxygen species (ROS) generation. Mechanically, THC administration remarkably increased the expression of the SIRT1 signaling pathway both in vitro and in vivo, further evidenced by decreased downstream molecule Ac-SOD2 and enhanced deacetylated production SOD2, which finally strengthened antioxidative stress capacity proven by repaired activities of SOD and GSH-Px and reduced MDA production. Additionally, THC treatment accomplished its antifibrotic effect by depressing the ROS-induced TGFβ1/Smad3 signaling pathway followed by reduced expression of cardiac fibrotic markers α-SMA, collagen I, and collagen III. Collectively, these finds demonstrated the therapeutic potential of THC treatment to alleviate DCM mainly by attenuating hyperglycemia-induced oxidative stress and fibrosis via activating the SIRT1 pathway.

scholarly journals A Protective Role of Paeoniflorin in Fluctuant Hyperglycemia-Induced Vascular Endothelial Injuries through Antioxidative and Anti-Inflammatory Effects and Reduction of PKCβ1

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jing-Shang Wang ◽  
Ye Huang ◽  
Shuping Zhang ◽  
Hui-Jun Yin ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Level ◽  
Umbilical Vein ◽  
Protective Role ◽  
Vascular Endothelial ◽  
Glucose Levels ◽  
Umbilical Vein Endothelial Cells

Hyperglycemia fluctuation is associated with diabetes mellitus (DM) complications when compared to persistent hyperglycemia. Previous studies have shown that paeoniflorin (PF), through its antiapoptosis, anti-inflammation, and antithrombotic properties, effectively protects against cardiovascular and cerebrovascular disease. However, the mechanism underlying the protection from PF against vascular injuries induced by hyperglycemia fluctuations remains poorly understood. Herein, we investigated the potential protective role of PF on human umbilical vein endothelial cells (HUVECs) subjected to intermittent glucose levels in vitro and in DM rats with fluctuating hyperglycemia in vivo. A remarkable increased apoptosis associated with elevated inflammation, increased oxidative stress, and high protein level of PKCβ1 was induced in HUVECs by intermittently changing glucose for 8 days, and PF recovered those detrimental changes. LY333531, a potent PKCβ1 inhibitor, and metformin manifested similar effects. Additionally, in DM rats with fluctuating hyperglycemia, PF protected against vascular damage as what has been observed in vitro. Taken together, PF attenuates the vascular injury induced by fluctuant hyperglycemia through oxidative stress inhibition, inflammatory reaction reduction, and PKCβ1 protein level repression, suggesting its perspective clinical usage.

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