Abstract 207: Unc-51-like Kinase 1 (ULK1) Plays A Crucial Role In Mitophagy In Cardiomyocytes

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Toshiro Saito ◽  
Junichi Sadoshima
Keyword(s):  
Glucose Deprivation ◽  
High Ratio ◽  
Control Mechanisms ◽  
Oxygen Species ◽  
Predominant Role ◽  
Mitochondrial Quality Control ◽  
Over Expression ◽  
Pathological Conditions

The mitochondrion is an essential organelle that supplies ATP in cardiomyocytes (CMs). However, damaged mitochondria are harmful via the production of reactive oxygen species and induction of apoptosis in pathological conditions. Therefore, quality of mitochondria should be controlled tightly through various mitochondrial quality control mechanisms. Mitochondrial autophagy (mitophagy) is considered an integral part of this mechanism, and recent investigations uncovered the role of PINK1 and Parkin in mitophagy. However, these observations were made under artificial conditions, such as over-expression of Parkin or treatment with CCCP, and thus the precise mechanism has not been fully elucidated in more pathophysiologically relevant conditions. Recent evidence suggests that mitophagy can take place independently of ATG7, a molecule essential for the conventional form of autophagy, and that this form of autophagy is ULK1-dependent. We investigated the role of ULK1 and ATG7 in mediating mitophagy using mitochondria-targeted Keima (Mito-Keima) in cultured rat neonatal CMs. Keima has a bimodal excitation spectrum peaking at 440 and 560 nm, corresponding to the neutral and acidic pH, respectively. In CMs transfected with Mito-Keima, the fluorescent dots with a high 560nm/440nm ratio represent the mitochondria incorporated into autolysosomes which indicate mitophagy. Here we report that ULK1 plays a more predominant role in glucose deprivation (GD) -induced mitophagy than ATG7. Control CMs exhibited 8.7±1.0 % of the area of high-ratio dots per cells after GD. Knockdown of ULK1 significantly reduced the area to 2.3±0.9 % in CMs after GD (p<0.01, vs sh-Control). The reduction was significantly greater in CMs with knockdown of ULK1 than that of ATG7 (7.0±1.6 %, p<0.05, sh-ULK1 vs sh-ATG7). In addition, knockdown of Beclin1 and Drp1 also significantly decreased the area of high-ratio dots (about 1.0 % and 0.5 %, respectively). Overexpression of ULK1 was sufficient to induce mitophagy without starvation, whereas that of ATG7 was not. These results suggest that ULK1, Beclin1 and Drp1 play an essential role in mediating GD-induced mitophagy in CMs.

scholarly journals Using Regulatory Flexibility to Address Market Informality in Seed Systems: A Global Study

Agronomy ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 377
Author(s):  
Katrin Kuhlmann ◽  
Bhramar Dey
Keyword(s):  
Seed Quality ◽  
Regulatory Environment ◽  
Control Mechanisms ◽  
Seed Systems ◽  
High Quality ◽  
Design And Implementation ◽  
Key Dimensions ◽  
Regulatory Flexibility

Seed rules and regulations determine who can produce and sell seeds, which varieties will be available in the market, the quality of seed for sale, and where seed can be bought and sold. The legal and regulatory environment for seed impacts all stakeholders, including those in the informal sector, through shaping who can participate in the market and the quality and diversity of seed available. This paper addresses a gap in the current literature regarding the role of law and regulation in linking the informal and formal seed sectors and creating more inclusive and better governed seed systems. Drawing upon insights from the literature, global case studies, key expert consultations, and a methodology on the design and implementation of law and regulation, we present a framework that evaluates how regulatory flexibility can be built into seed systems to address farmers’ needs and engage stakeholders of all sizes. Our study focuses on two key dimensions: extending market frontiers and liberalizing seed quality control mechanisms. We find that flexible regulatory approaches and practices play a central role in building bridges between formal and informal seed systems, guaranteeing quality seed in the market, and encouraging market entry for high-quality traditional and farmer-preferred varieties.

scholarly journals Antioxidant effect of Mn2+ on capacitation and acrosome reaction of fresh and chilled cattle bull semen

2012 ◽  
Vol 1 (1) ◽  
pp. 18
Author(s):  
Amrit Kaur Bansal ◽  
Ranjna Sundhey Cheema ◽  
Vinod Kumar Gandotra
Keyword(s):  
Reactive Oxygen Species ◽  
Lipid Peroxidation ◽  
Acrosome Reaction ◽  
Reactive Oxygen ◽  
Antioxidant Effect ◽  
Oxygen Species ◽  
Sperm Capacitation ◽  
Bull Semen

The aim of this paper was to investigate the antioxidant effect of Mn2+ (200 mM) on the sperm capacitation and acrosome reaction of fresh and chilled cattle bull semen. It has been found that Mn2+ supplementation improves (P≤0.05) the motility at 0, 2, 4 and 6 h of incubation. MDA (malondialdehyde), end product of lipid peroxidation, decreases significantly (P≤0.05) with the supplementation of manganese at 0- and 6-hr of incubation both in fresh and chilled semen. Manganese also increases acrosome reaction significantly (P≤0.05) both in fresh and chilled semen at 0, 4 and 6 h of incubation. Therefore, our findings suggest the role of Mn2+supplementation in improving the quality of cattle bull semen by its scavenging property<em> i.e.</em> reduction in the production of reactive oxygen species during its storage at 4°C or incubation at 37°C for capacitation.

Superoxide Production by the Mitochondrial Respiratory Chain

1997 ◽  
Vol 17 (1) ◽  
pp. 3-8 ◽  
Author(s):  
Julio F. Turrens
Keyword(s):  
Reactive Oxygen Species ◽  
Respiratory Chain ◽  
Reactive Oxygen ◽  
Mitochondrial Respiratory Chain ◽  
Superoxide Production ◽  
Oxygen Species ◽  
Pathological Conditions ◽  
Superoxide Formation ◽  
Effect Of Inhibitors

This mini-review describes the role of different mitochondrial components in the formation of reactive oxygen species under normal and pathological conditions and the effect of inhibitors and uncouplers on superoxide formation.

scholarly journals PINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
So-Young Lee ◽  
Hyun-Ju An ◽  
Jin Man Kim ◽  
Min-Ji Sung ◽  
Do Kyung Kim ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Quality Control ◽  
Reactive Oxygen Species Production ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Homeostasis ◽  
Ovariectomized Mice ◽  
Species Production

Abstract Background PTEN-induced kinase 1 (PINK1) is a serine/threonine-protein kinase in mitochondria that is critical for mitochondrial quality control. PINK1 triggers mitophagy, a selective autophagy of mitochondria, and is involved in mitochondrial regeneration. Although increments of mitochondrial biogenesis and activity are known to be crucial during differentiation, data regarding the specific role of PINK1 in osteogenic maturation and bone remodeling are limited. Methods We adopted an ovariectomy model in female wildtype and Pink1−/− mice. Ovariectomized mice were analyzed using micro-CT, H&E staining, Masson’s trichrome staining. RT-PCR, western blot, immunofluorescence, alkaline phosphatase, and alizarin red staining were performed to assess the expression of PINK1 and osteogenic markers in silencing of PINK1 MC3T3-E1 cells. Clinical relevance of PINK1 expression levels was determined via qRT-PCR analysis in normal and osteoporosis patients. Results A significant decrease in bone mass and collagen deposition was observed in the femurs of Pink1−/− mice after ovariectomy. Ex vivo, differentiation of osteoblasts was inhibited upon Pink1 downregulation, accompanied by impaired mitochondrial homeostasis, increased mitochondrial reactive oxygen species production, and defects in mitochondrial calcium handling. Furthermore, PINK1 expression was reduced in bones from patients with osteoporosis, which supports the practical role of PINK1 in human bone disease. Conclusions In this study, we demonstrated that activation of PINK1 is a requisite in osteoblasts during differentiation, which is related to mitochondrial quality control and low reactive oxygen species production. Enhancing PINK1 activity might be a possible treatment target in bone diseases as it can promote a healthy pool of functional mitochondria in osteoblasts.

Pesticides-induced cardiovascular dysfunctions: Prevalence and associated mechanisms

2021 ◽  
Vol 17 ◽  
Author(s):  
Joseph A. Adeyemi ◽  
Victor O. Ukwenya ◽  
Olatunbosun K. Arowolo ◽  
Christian C. Olise
Keyword(s):  
Public Health ◽  
Oxidative Stress ◽  
Risk Factors ◽  
Cardiovascular Diseases ◽  
Chronic Exposure ◽  
Human Exposure ◽  
Laboratory Data ◽  
Oxygen Species ◽  
Pathological Conditions

: Increased applications of pesticides mainly in agriculture and public health has resulted in increased chances of human exposure to pesticides. Chronic exposure to pesticides has been implicated in several human diseases including cardiovascular diseases. Cardiovascular diseases are broadly used for various heart pathological conditions including defect blood vessels, and they include myocardial infarction, atherosclerosis, stroke, cardiomyopathy, coronary heart disease etc. In this review, the association between human exposure to pesticides and development of cardiovascular diseases was discussed using epidemiological and laboratory data. The toxicokinetics of pesticides in humans was reviewed, as well as the risk factors for cardiovascular diseases. The important role of oxidative stress, and principally the induction of reactive oxygen species as the signaling molecules for various signaling pathways involved in pesticidesinduced cardiovascular disease was discussed.

scholarly journals Defective Autophagy in Atherosclerosis: To Die or to Senesce?

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Mandy O. J. Grootaert ◽  
Lynn Roth ◽  
Dorien M. Schrijvers ◽  
Guido R. Y. De Meyer ◽  
Wim Martinet
Keyword(s):  
Cell Types ◽  
Special Focus ◽  
Oxygen Species ◽  
Cell Type ◽  
Mitochondrial Quality Control ◽  
Targeted Treatments ◽  
Wide Range ◽  
Autophagic Process ◽  
Progression Of Atherosclerosis

Autophagy is a subcellular process that plays an important role in the degradation of proteins and damaged organelles such as mitochondria (a process termed “mitophagy”) via lysosomes. It is crucial for regulating protein and mitochondrial quality control and maintaining cellular homeostasis, whereas dysregulation of autophagy has been implicated in a wide range of diseases including atherosclerosis. Recent evidence has shown that the autophagic process becomes dysfunctional during the progression of atherosclerosis, regardless of whether there are many autophagy-stimulating factors (e.g., reactive oxygen species, oxidized lipids, and cytokines) present within the atherosclerotic plaque. This review highlights the recent insights into the causes and consequences of defective autophagy in atherosclerosis, with a special focus on the role of autophagy and mitophagy in plaque macrophages, vascular smooth muscle cells (VSMCs), and endothelial cells (ECs). It has been shown that defective autophagy can promote apoptosis in macrophages but that it accelerates premature senescence in VSMCs. In the ECs, defective autophagy promotes both apoptosis and senescence. We will discuss the discrepancy between these three cell types in their response to autophagy deficiency and underline the cell type-dependent role of autophagy, which may have important implications for the efficacy of autophagy-targeted treatments for atherosclerosis.

scholarly journals Molecules and Mechanisms to Overcome Oxidative Stress Inducing Cardiovascular Disease in Cancer Patients

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 105
Author(s):  
Francesco Sabbatino ◽  
Valeria Conti ◽  
Luigi Liguori ◽  
Giovanna Polcaro ◽  
Graziamaria Corbi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Ros Production ◽  
Oxygen Species ◽  
Physiological Conditions ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
Detoxification Systems ◽  
Cancer Diseases

Reactive oxygen species (ROS) are molecules involved in signal transduction pathways with both beneficial and detrimental effects on human cells. ROS are generated by many cellular processes including mitochondrial respiration, metabolism and enzymatic activities. In physiological conditions, ROS levels are well-balanced by antioxidative detoxification systems. In contrast, in pathological conditions such as cardiovascular, neurological and cancer diseases, ROS production exceeds the antioxidative detoxification capacity of cells, leading to cellular damages and death. In this review, we will first describe the biology and mechanisms of ROS mediated oxidative stress in cardiovascular disease. Second, we will review the role of oxidative stress mediated by oncological treatments in inducing cardiovascular disease. Lastly, we will discuss the strategies that potentially counteract the oxidative stress in order to fight the onset and progression of cardiovascular disease, including that induced by oncological treatments.

scholarly journals Polyamines accentuate vase life by augmenting antioxidant system in cut spikes of Consolida ajacis (L.) Schur.

2021 ◽  
Vol 27 (4) ◽  
pp. 495-504
Author(s):  
Aehsan ul Haq ◽  
Sumira Farooq ◽  
Mohammad Lateef Lone ◽  
Shazia Parveen ◽  
Foziya Altaf ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Postharvest Quality ◽  
Flower Senescence ◽  
Vase Life ◽  
Distilled Water ◽  
Oxygen Species ◽  
Cut Flowers ◽  
Postharvest Senescence

Abstract Postharvest senescence is one of the crucial challenges limiting the marketability of cut flowers. Pertinently, recent investigations implicate extensive role of polyamines in regulation of flower senescence. The present study was envisaged to test the efficacy of poylamines in preserving the postharvest quality of Consolida ajacis (C. ajacis) cut spikes. The cut spikes of C. ajacis were subjected to various treatments of polyamines viz, 4 mM Spermine (SPM), 6mM Putrescine (PUT) and 6 mM Spermidine (SPD). A separate set of spikes held in distilled water represented the control. Our results authenticate a significant improvement in vase life of cut spikes of C. ajacis as compared to control. The increment in vase life was commensurate with the higher concentration of sugars, proteins and phenols in the tepal tissues. Polyamines amplified the activity of various antioxidant enzymes viz, superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) to overcome the deleterious effects of reactive oxygen species (ROS). The membrane outflow of tepal tissues was profoundly reduced due to attenuated lipoxygenase (LOX) activity. These findings reveal conspicuous role of polyamines particularly SPM in modulation of flower senescence in cut spikes of C. ajacis.

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