scholarly journals BNIP3L/NIX-mediated mitophagy protects against glucocorticoid-induced synapse defects

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Gee Euhn Choi ◽  
Hyun Jik Lee ◽  
Chang Woo Chae ◽  
Ji Hyeon Cho ◽  
Young Hyun Jung ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Nuclear Translocation ◽  
Memory Task ◽  
Mitochondrial Bioenergetics ◽  
Synaptic Density ◽  
Spatial Memory Task ◽  
Vesicle Recycling ◽  
Pre Treatment ◽  
Respiration Function

AbstractStress-induced glucocorticoids disturb mitochondrial bioenergetics and dynamics; however, instead of being removed via mitophagy, the damaged mitochondria accumulate. Therefore, we investigate the role of glucocorticoids in mitophagy inhibition and subsequent synaptic defects in hippocampal neurons, SH-SY5Y cells, and ICR mice. First, we observe that glucocorticoids decrease both synaptic density and vesicle recycling due to suppressed mitophagy. Screening data reveal that glucocorticoids downregulate BNIP3-like (BNIP3L)/NIX, resulting in the reduced mitochondrial respiration function and synaptic density. Notably, we find that glucocorticoids direct the glucocorticoid receptor to bind directly to the PGC1α promoter, downregulating its expression and nuclear translocation. PGC1α downregulation selectively decreases NIX-dependent mitophagy. Consistent with these results, NIX enhancer pre-treatment of a corticosterone-exposed mouse elevates mitophagy and synaptic density in hippocampus, improving the outcome of a spatial memory task. In conclusion, glucocorticoids inhibit mitophagy via downregulating NIX and that NIX activation represents a potential target for restoring synapse function.

scholarly journals Inhibition of histone deacetylase protects the damaged cataract via regulating the NF-κB pathway in cultured lens epithelial cells

2019 ◽  
Vol 17 ◽  
pp. 205873921987009
Author(s):  
Jun Liu ◽  
Yan Yin
Keyword(s):  
Epithelial Cells ◽  
Histone Deacetylase ◽  
Nuclear Translocation ◽  
Trichostatin A ◽  
Membrane Damage ◽  
Hdac Inhibitors ◽  
Nuclear Factor Κb ◽  
Pre Treatment ◽  
In Cells

Induction of oxidative damage by the activation of histone deacetylase (HDAC) is an integral event that causes major membrane damage of ocular tissues and leads to the pathogenesis of cataract. It is elucidated that nuclear factor-κB is a mediator in the process of cataract development. However, studies on the role played by epigenetic proteins in regulating cataract pathogenesis are limited. Hence, in the current investigation, ARPE-19 human retinal epithelial cells were used as an experimental model to elucidate the role of HDAC inhibition and its mechanism behind the cataract pathogenesis. ARPE-19 cells were exposed to H2O2, with and without Trichostatin A (TSA), a pan-HDAC inhibitor, and maintained along with control cells without any treatment. On exposure to H2O2, cells were susceptible to oxidative stress as it is evident from the reduced expression levels of superoxide dismutase (SOD), catalase, and GSH levels. Simultaneously, H2O2-exposed cells showed the nuclear translocation of NF-κB with the activation of inflammatory cytokines such as CXCL1 and IL-6. In addition, the mRNA expression analysis revealed that the GADD45α, COX-2, MCP-1, and ICAM-1 expressions were increased in H2O2 group. Moreover, the activity of HDAC was increased to 2-fold with a significant reduction in the histone acetyltransferase (HAT) activity in cells that were maintained under oxidative conditions. However, TSA was able to inhibit the critical cytokines’ expression with attenuated HDAC activity and limited NF-κB translocation. Furthermore, pre-treatment of TSA significantly suppressed the transcript levels of up-regulated inflammatory markers in cells. Together, these findings offer new insight into the role of HDACs in regulating cellular processes involved in the pathogenesis of cataract as well as the potential use of HDAC inhibitors as therapeutics for controlling the disease progression.

scholarly journals Flexible coding of memory and space in the primate hippocampus during virtual navigation

2018 ◽  
Author(s):  
Roberto A. Gulli ◽  
Lyndon Duong ◽  
Ben Corrigan ◽  
Guillaume Doucet ◽  
Sylvain Williams ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Memory Task ◽  
Memory Storage ◽  
Virtual Navigation ◽  
Spatial Features ◽  
Recorded Activity ◽  
Efficient Memory ◽  
Foraging Task ◽  
Object Association

AbstractHippocampal maps of space change across tasks. The mechanisms of this effect remain unclear. To examine this, we recorded activity of hippocampal neurons in monkeys navigating the same virtual maze during two different tasks: a foraging task requiring only cue guided navigation, and a memory task also requiring context-object association. Within each task, individual neurons had spatially-selective response fields, enabling a linear classifier to decode position in the virtual environment in each task. However, the population code did not generalize across tasks. This was due to sensory and mnemonic coding of non-spatial features and their associations by single neurons during each period of the associative memory task. Thus, sensory and mnemonic representations of non-spatial features shape maps of space in the primate hippocampus during virtual navigation. This may reflect a fundamental role of the hippocampus in compressing information from a variety of sources for efficient memory storage.

Allocentric to Egocentric Spatial Switching: Impairment in aMCI and Alzheimer's Disease Patients?

2018 ◽  
Vol 15 (3) ◽  
pp. 229-236 ◽  
Author(s):  
Gennaro Ruggiero ◽  
Alessandro Iavarone ◽  
Tina Iachini
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Reference Frame ◽  
Reference Frames ◽  
Memory Task ◽  
Spatial Representations ◽  
The Novel ◽  
Spatial Memory Task ◽  
Switching Condition ◽  
Normal Controls

Objective: Deficits in egocentric (subject-to-object) and allocentric (object-to-object) spatial representations, with a mainly allocentric impairment, characterize the first stages of the Alzheimer's disease (AD). Methods: To identify early cognitive signs of AD conversion, some studies focused on amnestic-Mild Cognitive Impairment (aMCI) by reporting alterations in both reference frames, especially the allocentric ones. However, spatial environments in which we move need the cooperation of both reference frames. Such cooperating processes imply that we constantly switch from allocentric to egocentric frames and vice versa. This raises the question of whether alterations of switching abilities might also characterize an early cognitive marker of AD, potentially suitable to detect the conversion from aMCI to dementia. Here, we compared AD and aMCI patients with Normal Controls (NC) on the Ego-Allo- Switching spatial memory task. The task assessed the capacity to use switching (Ego-Allo, Allo-Ego) and non-switching (Ego-Ego, Allo-Allo) verbal judgments about relative distances between memorized stimuli. Results: The novel finding of this study is the neat impairment shown by aMCI and AD in switching from allocentric to egocentric reference frames. Interestingly, in aMCI when the first reference frame was egocentric, the allocentric deficit appeared attenuated. Conclusion: This led us to conclude that allocentric deficits are not always clinically detectable in aMCI since the impairments could be masked when the first reference frame was body-centred. Alongside, AD and aMCI also revealed allocentric deficits in the non-switching condition. These findings suggest that switching alterations would emerge from impairments in hippocampal and posteromedial areas and from concurrent dysregulations in the locus coeruleus-noradrenaline system or pre-frontal cortex.

scholarly journals Membrane condenser as emerging technology for water recovery and gas pre-treatment: current status and perspectives

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Adele Brunetti ◽  
Francesca Macedonio ◽  
Giuseppe Barbieri ◽  
Enrico Drioli
Keyword(s):  
Current Status ◽  
Innovative Technology ◽  
Water Recovery ◽  
Treatment Unit ◽  
Treatment Stage ◽  
Treatment Technologies ◽  
Pre Treatment ◽  
And Control

Abstract The recent roadmap of SPIRE initiative includes the development of “new separation, extraction and pre-treatment technologies” as one of the “key actions” for boosting sustainability, enhancing the availability and quality of existing resources. Membrane condenser is an innovative technology that was recently investigated for the recovery of water vapor for waste gaseous streams, such as flue gas, biogas, cooling tower plumes, etc. Recently, it has been also proposed as pre-treatment unit for the reduction and control of contaminants in waste gaseous streams (SOx and NOx, VOCs, H2S, NH3, siloxanes, halides, particulates, organic pollutants). This perspective article reports recent progresses in the applications of the membrane condenser in the treatment of various gaseous streams for water recovery and contaminant control. After an overview of the operating principle, the membranes used, and the main results achieved, the work also proposes the role of this technology as pre-treatment stage to other separation technologies. The potentialities of the technology are also discussed aspiring to pave the way towards the development of an innovative technology where membrane condenser can cover a key role in redesigning the whole upgrading process.

scholarly journals EGFR-ERK induced activation of GRHL1 promotes cell cycle progression by up-regulating cell cycle related genes in lung cancer

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Yiming He ◽  
Mingxi Gan ◽  
Yanan Wang ◽  
Tong Huang ◽  
Jianbin Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Potential Role ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Phosphorylation Site ◽  
Promoter Regions ◽  
Cycle Progression

AbstractGrainyhead-like 1 (GRHL1) is a transcription factor involved in embryonic development. However, little is known about the biological functions of GRHL1 in cancer. In this study, we found that GRHL1 was upregulated in non-small cell lung cancer (NSCLC) and correlated with poor survival of patients. GRHL1 overexpression promoted the proliferation of NSCLC cells and knocking down GRHL1 inhibited the proliferation. RNA sequencing showed that a series of cell cycle-related genes were altered when knocking down GRHL1. We further demonstrated that GRHL1 could regulate the expression of cell cycle-related genes by binding to the promoter regions and increasing the transcription of the target genes. Besides, we also found that EGF stimulation could activate GRHL1 and promoted its nuclear translocation. We identified the key phosphorylation site at Ser76 on GRHL1 that is regulated by the EGFR-ERK axis. Taken together, these findings elucidate a new function of GRHL1 on regulating the cell cycle progression and point out the potential role of GRHL1 as a drug target in NSCLC.

scholarly journals Phaseolin Attenuates Lipopolysaccharide-Induced Inflammation in RAW 264.7 Cells and Zebrafish

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 420
Author(s):  
Su-Jung Hwang ◽  
Ye-Seul Song ◽  
Hyo-Jong Lee
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Raw 264.7 Cells ◽  
Network Pharmacology ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Bioactive Constituents

Kushen (Radix Sophorae flavescentis) is used to treat ulcerative colitis, tumors, and pruritus. Recently, phaseolin, formononetin, matrine, luteolin, and quercetin, through a network pharmacology approach, were tentatively identified as five bioactive constituents responsible for the anti-inflammatory effects of S. flavescentis. However, the role of phaseolin (one of the primary components of S. flavescentis) in the direct regulation of inflammation and inflammatory processes is not well known. In this study, the beneficial role of phaseolin against inflammation was explored in lipopolysaccharide (LPS)-induced inflammation models of RAW 264.7 macrophages and zebrafish larvae. Phaseolin inhibited LPS-mediated production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), without affecting cell viability. In addition, phaseolin suppressed pro-inflammatory mediators such as cyclooxygenase 2 (COX-2), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in a dose-dependent manner. Furthermore, phaseolin reduced matrix metalloproteinase (MMP) activity as well as macrophage adhesion in vitro and the recruitment of leukocytes in vivo by downregulating Ninjurin 1 (Ninj1), an adhesion molecule. Finally, phaseolin inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB). In view of the above, our results suggest that phaseolin could be a potential therapeutic candidate for the management of inflammation.

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