scholarly journals Protective role of mRNA demethylase FTO on axon guiding molecules of nigro-striatal projection system in manganese-induced Parkinsonism

2021 ◽  
Author(s):  
Zhipeng Qi ◽  
Jiashuo Li ◽  
Ke Zhang ◽  
Yanan Liu ◽  
Xinxin Yang ◽  
...  
Keyword(s):  
Therapeutic Response ◽  
Axon Growth ◽  
Protective Role ◽  
Motor Dysfunction ◽  
Exposure Model ◽  
Domain Family ◽  
Projection System ◽  
Over Expression ◽  
Target Indicator

Abstract Background Parkinson's disease (PD) is a neurodegenerative disease caused by environmental and genetic factors. Manganese (Mn) exposure is a major environmental cause of PD. Cellular and molecular mechanism of Parkinsonism caused by Mn has not been explored clearly. In addition, patients with Mn-induced Parkinsonism show poor therapeutic response to levodopa. Therefore, there is need to explore the mechanisms underlying neurotoxicity of Mn exposure. Methods In short, we used SH-SY5Y cells and C57BL/6 mice to characterize Mn-induced Parkinsonism. We measured the behavioral, histological, ultrastructural and nigro-striatal projection system changes, cell viability, axon growth, and other target indicator levels, which led to the discovery of a novel mechanism of Mn-induced neurotoxicity. Results The findings of the current study showed that inhibition of fat mass and obesity-associated protein (FTO)-mediated demethylation of N6-methyladenosine (m6A) mRNA aggravates Mn-induced motor dysfunction. Notably, FTO level is low in Mn exposure model mice and enhances occurrence of dyskinesia in mice. Over-expression of FTO reduces m6A methylation in the key axon guiding molecules of nigro-striatal projection system, including ephrin-A5 and ephrin-B2. It increases ephrin-B2 mRNA decay through the m6A reader YT521-B homology domain family proteins 2 (YTHDF2). Conclusions The findings of this study show that FTO, a m6A demethylase, performs an indispensable function in Mn-induced Parkinsonism. Notably, re-expression of FTO and ephrin-B2 improved motor dysfunction after Mn exposure.

scholarly journals Protective Role of Selenium Against Over-Expression of Cancer-Related Apoptotic Genes Induced By O-Cresol in Rats

2011 ◽  
Vol 62 (2) ◽  
pp. 121-129 ◽  
Author(s):  
Wagdy Khalil ◽  
Hoda Booles
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Protective Role ◽  
Male Rats ◽  
Control Group ◽  
Tissue Samples ◽  
Over Expression ◽  
Apoptotic Genes

Protective Role of Selenium Against Over-Expression of Cancer-Related Apoptotic Genes Induced By O-Cresol in RatsCresols are monomethyl derivatives of phenol frequently used as solvents and intermediates in the production of disinfectants, fragrances, pesticides, dyes, and explosives, which is probably why they are widely distributed in the environment. General population may be exposed to cresols mainly through inhalation of contaminated air. In this study we evaluated the toxicological effects of o-cresol on differential gene expression profile of rat liver and prostate. Experiments were conducted on 80 male rats, 60 of which were exposed to o-cresol (1.5 g kg-1, 5 g kg-1, or 15 g kg-1) through feed for 8 weeks. Three groups of rats were supplemented with 0.1 mg kg-1 selenium (Se, in the form of, sodium selenite) in addition to o-cresol to evaluate its effectiveness against o-cresol toxicity. Control group received neither o-cresol nor Se, while one group received Se alone. Survival was similar between the exposed and control animals. Rats exposed to 15 g kg-1 of o-cresol showed a 16 % loss in body weight by the end of the study, which may have been related to o-cresol making feed unpalatable at this concentration. Liver and prostate tissue samples were collected at the end of the treatment. mRNA analysis revealed that apoptotic genes (CYP3A, COX-2, PPARγ, BAX, BCL2, AKT-1, and PKCα) related to cancer were up-regulated in liver and prostate tissues isolated from groups exposed to 5 g kg-1 and 15 g kg-1o-cresol in comparison to control. Changes in gene expression profile were prevented when rats were supplemented with Se. The exact mechanisms underlying its protective effect remain to be clarified by future studies.

scholarly journals Mannose-binding lectin reduces oxidized low-density lipoprotein induced vascular endothelial cells injury by modulating autophagy via LOX1

2021 ◽  
Author(s):  
Xue-lian Zhou ◽  
Xue-feng Chen ◽  
Li Zhang ◽  
Jin-na Yuan ◽  
Hu Lin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Protective Role ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Over Expression ◽  
Mannose Binding ◽  
Binding Lectin

Abstract Objective To investigate the role of mannose-binding lectin (MBL) in modulating autophagy and protecting endothelial cells (ECs) from oxidized low-density lipoprotein (ox-LDL) induced injury. Materials and Methods Rapamycin and chloroquine were used to confirm the role of autophagy in ox-LDL induced ECs injury. Dendritic cells (DCs) were co-cultured with ECs, after which inflammatory factors and DCs maturation rate were detected. Autophagy was detected by LC3 and Lamp2a or autophagosomes. Cell viability was analyzed by Cell Counting Kit-8 (CCK-8) assay. Flow cytometry was utilized to analyze cell proliferation and apoptotic rate. ECs transfected with lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)-siRNA or MBL over-expression plasmid were treated with ox-LDL to explore the mechanism of MBL in ECs injury. HE, Oil Red O, TUNEL staining, and immunofluorescence were used to evaluate the atherosclerotic plaque, ECs injury, and autophagy, respectively. Retro-eyeball injections of MBL over-expression adenovirus were conducted every 4 weeks, after which ECs injury, autophagy, the uptake of ox-LDL, and expression of LOX1 were further analyzed. Results ECs treated with 100 ug/mL ox-LDL for 24 h significantly increased the expression of LC3, Lamp2a, and ET1. Rapamycin aggravated, chloroquine alleviated ox-LDL induced ECs autophagy and injury. LOX1-siRNA transfected ECs inhibited the uptake of ox-LDL and reduced ECs autophagy and injury compared with siRNA group. MBL over-expression in vitro decreased the binding of LOX1 and ox-LDL, ameliorated ECs autophagy and injury compared with the control plasmid group. MBL over-expression in vivo alleviated the formation of atherosclerotic plaque in HFD fed ApoE-/- mice, influenced the maturation of DCs, and down-regulated IL-6, IL-12, and TNF-a level compared with the control group. Also, mannan could reverse the protective role of MBL. Conclusion MBL exerts a protective role in ox-LDL induced ECs injury and HFD induced atherosclerosis model by regulating DCs maturation and modulating ECs autophagy via blocking the binding of LOX1 and ox-LDL.

Protective role of peroxiredoxin-4 in heart failure

2020 ◽  
Vol 134 (1) ◽  
pp. 71-72
Author(s):  
Naseer Ahmed ◽  
Masooma Naseem ◽  
Javeria Farooq
Keyword(s):  
Heart Failure ◽  
Cardiac Fibroblasts ◽  
Protective Role ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Total Antioxidant ◽  
Galectin 3 ◽  
Consequent Increase ◽  
And Oxidative Stress

Abstract Recently, we have read with great interest the article published by Ibarrola et al. (Clin. Sci. (Lond.) (2018) 132, 1471–1485), which used proteomics and immunodetection methods to show that Galectin-3 (Gal-3) down-regulated the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. Authors concluded that ‘antioxidant activity of Prx-4 had been identified as a protein down-regulated by Gal-3. Moreover, Gal-3 induced a decrease in total antioxidant capacity which resulted in a consequent increase in peroxide levels and oxidative stress markers in cardiac fibroblasts.’ We would like to point out some results stated in the article that need further investigation and more detailed discussion to clarify certain factors involved in the protective role of Prx-4 in heart failure.

Parenting Behaviors and Anxiety in Young Adults

2015 ◽  
Vol 36 (3) ◽  
pp. 170-176 ◽  
Author(s):  
Erin N. Stevens ◽  
Joseph R. Bardeen ◽  
Kyle W. Murdock
Keyword(s):  
Effortful Control ◽  
Parenting Behaviors ◽  
Protective Role ◽  
Anxiety Symptoms ◽  
Interactive Effects ◽  
Parental Overprotection ◽  
High Control ◽  
Development Of Anxiety ◽  
The Relationship

Parenting behaviors – specifically behaviors characterized by high control, intrusiveness, rejection, and overprotection – and effortful control have each been implicated in the development of anxiety pathology. However, little research has examined the protective role of effortful control in the relation between parenting and anxiety symptoms, specifically among adults. Thus, we sought to explore the unique and interactive effects of parenting and effortful control on anxiety among adults (N = 162). Results suggest that effortful control uniquely contributes to anxiety symptoms above and beyond that of any parenting behavior. Furthermore, effortful control acted as a moderator of the relationship between parental overprotection and anxiety, such that overprotection is associated with anxiety only in individuals with lower levels of effortful control. Implications for potential prevention and intervention efforts which specifically target effortful control are discussed. These findings underscore the importance of considering individual differences in self-regulatory abilities when examining associations between putative early-life risk factors, such as parenting, and anxiety symptoms.

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