scholarly journals Targeting Microglial KATPChannels to Treat Neurodegenerative Diseases: A Mitochondrial Issue

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Manuel J. Rodríguez ◽  
Margot Martínez-Moreno ◽  
Francisco J. Ortega ◽  
Nicole Mahy
Keyword(s):  
Energy Demand ◽  
Dynamic Equilibrium ◽  
Cell Types ◽  
High Energy ◽  
Mitochondrial Activity ◽  
Matrix Remodeling ◽  
Cellular Processes ◽  
Neurodegenerative Process ◽  
Response Capacity ◽  
Unique Cell

Neurodegeneration is a complex process involving different cell types and neurotransmitters. A common characteristic of neurodegenerative disorders is the occurrence of a neuroinflammatory reaction in which cellular processes involving glial cells, mainly microglia and astrocytes, are activated in response to neuronal death. Microglia do not constitute a unique cell population but rather present a range of phenotypes closely related to the evolution of neurodegeneration. In a dynamic equilibrium with the lesion microenvironment, microglia phenotypes cover from a proinflammatory activation state to a neurotrophic one directly involved in cell repair and extracellular matrix remodeling. At each moment, the microglial phenotype is likely to depend on the diversity of signals from the environment and of its response capacity. As a consequence, microglia present a high energy demand, for which the mitochondria activity determines the microglia participation in the neurodegenerative process. As such, modulation of microglia activity by controlling microglia mitochondrial activity constitutes an innovative approach to interfere in the neurodegenerative process. In this review, we discuss the mitochondrial KATPchannel as a new target to control microglia activity, avoid its toxic phenotype, and facilitate a positive disease outcome.

Stretch-Activated Calcium Signal Propagation Following Mechanical Stimulation of Focal Adhesions

2007 ◽  
Author(s):  
Warren C. Ruder ◽  
Erica D. Pratt ◽  
Nailah Z. Brandy ◽  
David A. LaVan ◽  
Philip R. LeDuc ◽  
...  
Keyword(s):  
Mechanical Stimulation ◽  
Focal Adhesions ◽  
Signal Propagation ◽  
Cell Types ◽  
Calcium Signal ◽  
Matrix Remodeling ◽  
Mechanical Stimuli ◽  
Cellular Processes ◽  
Unique Manner ◽  
Tissue Matrix

Cells translate environmental mechanical stimuli into biochemical reactions that govern a range of cellular processes such as proliferation, death and tissue matrix remodeling. Mechanical activation of individual focal adhesions formed between the cell and its environment directly correspond to several internal responses. Intracellular calcium concentration, [Ca2+]in, has been shown to profoundly change during force sensing. In order to understand this dynamic in cells, we compared calcium mobilization resulting from chemical stimulation and that resulting from mechanical stimulation. We have analyzed the response of fibroblasts to membrane displacements of over 5 μm resulting in eventual spikes in [Ca2+]in. Our data initially indicates that fibroblasts may process mechanical calcium events in unique manner in comparison to other cell types. This finding has implications in a range of fields including mechanobiology and magnetics based activation.

scholarly journals Hypoxia-Inducible Factor and Oxygen Biology in the Kidney

Kidney360 ◽  
2020 ◽  
Vol 1 (9) ◽  
pp. 1021-1031
Author(s):  
Mai Sugahara ◽  
Tetsuhiro Tanaka ◽  
Masaomi Nangaku
Keyword(s):  
Energy Demand ◽  
Kidney Diseases ◽  
Hypoxia Inducible Factor ◽  
Kidney Tissue ◽  
Renal Medulla ◽  
Cell Types ◽  
High Energy ◽  
Adaptation To Hypoxia ◽  
Specific Context ◽  
Capillary Rarefaction

Kidney tissue hypoxia is detected in various kidney diseases and is considered to play an important role in the pathophysiology of both AKI and CKD. Because of the characteristic vascular architecture and high energy demand to drive tubular solute transport, the renal medulla is especially prone to hypoxia. Injured kidneys often present capillary rarefaction, inflammation, and fibrosis, which contribute to sustained kidney hypoxia, forming a vicious cycle promoting progressive CKD. Hypoxia-inducible factor (HIF), a transcription factor responsible for cellular adaptation to hypoxia, is generally considered to protect against AKI. On the contrary, consequences of sustained HIF activation in CKD may be either protective, neutral, or detrimental. The kidney outcomes seem to be affected by various factors, such as cell types in which HIF is activated/inhibited, disease models, balance between two HIF isoforms, and time and methods of intervention. This suggests multifaceted functions of HIF and highlights the importance of understanding its role within each specific context. Prolyl-hydroxylase domain (PHD) inhibitors, which act as HIF stabilizers, have been developed to treat anemia of CKD. Although many preclinical studies demonstrated renoprotective effects of PHD inhibitors in CKD models, there may be some situations in which they lead to deleterious effects. Further studies are needed to identify patients who would gain additional benefits from PHD inhibitors and those who may need to avoid them.

scholarly journals Distinct mitochondrial remodeling during early cardiomyocyte development in a human-based stem cell model

2021 ◽  
Author(s):  
Sepideh Mostafavi ◽  
Novin Balafkan ◽  
Ina Katrine Nitschke Pettersen ◽  
Gonzalo S. Nido ◽  
Richard Siller ◽  
...  
Keyword(s):  
Energy Demand ◽  
Cell Model ◽  
Energy Requirement ◽  
Mitochondrial Respiratory Chain ◽  
High Energy ◽  
Mitochondrial Activity ◽  
Cardiomyocyte Differentiation ◽  
Mitochondrial Content ◽  
Activity Increase ◽  
Cardiac Progenitors

Post-mitotic tissues with high-energy demand rely on ATP generated by the mitochondrial respiratory chain through the process of oxidative phosphorylation (OXPHOS). There is common agreement that mitochondrial content and OXPHOS activity increase as cells exit from pluripotency state to meet the higher energy requirement of differentiated tissues such as heart. In this study, we examined the hypothesis that mitochondrial expansion during differentiation is necessary to compensate for higher energy demand in differentiated cells. We assessed mitochondrial and cellular metabolism during differentiation of human pluripotent stem cells to cardiac progenitors and further to functional cardiomyocytes. Contrary to expectations, we found that mitochondrial content decreased progressively during mesoderm differentiation. Nevertheless, we found that there was increased mitochondrial activity and higher levels of ATP-linked respiration, which we suggest more than compensate for the lower mitochondrial number. Our findings support a model whereby mitochondrial maturation during cardiomyocyte differentiation depends on increased efficiency of ATP generation through OXPHOS not increased mitochondrial biogenesis. Thus, the timing of the mitochondria expansion during cardiomyocyte differentiation will have to be revisited in light of these findings.

Changes in lipid peroxidation during pregnancy and after delivery in rats: effect of pinealectomy

Reproduction ◽  
2000 ◽  
pp. 143-149 ◽  
Author(s):  
RM Sainz ◽  
RJ Reiter ◽  
JC Mayo ◽  
J Cabrera ◽  
DX Tan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Oxidative Damage ◽  
Energy Demand ◽  
Physiological State ◽  
High Energy ◽  
Free Radical Scavengers ◽  
Radical Scavengers ◽  
Oxygen Requirement ◽  
Pregnant Rats

Pregnancy is a physiological state accompanied by a high energy demand of many bodily functions and an increased oxygen requirement. Because of the increased intake and utilization of oxygen, increased levels of oxidative stress would be expected. In the present study, the degree of lipid peroxidation was examined in different tissues from non-pregnant and pregnant rats after the delivery of their young. Melatonin and other indole metabolites are known to be direct free radical scavengers and indirect antioxidants. Thus the effect of pinealectomy at 1 month before pregnancy on the accumulation of lipid damage was investigated in non-pregnant and pregnant rats after the delivery of their young. Malonaldehyde and 4-hydroxyalkenal concentrations were measured in the lung, uterus, liver, brain, kidney, thymus and spleen from intact and pinealectomized pregnant rats soon after birth of their young and at 14 and 21 days after delivery. The same parameters were also evaluated in intact and pinealectomized non-pregnant rats. Shortly after delivery, lipid oxidative damage was increased in lung, uterus, brain, kidney and thymus of the mothers. No differences were detected in liver and spleen. Pinealectomy enhanced this effect in the uterus and lung. It is concluded that during pregnancy high levels of oxidative stress induce an increase in oxidative damage to lipids, which in some cases is inhibited by the antioxidative actions of pineal indoles.

scholarly journals Mitochondrial Glucocorticoid Receptors and Their Actions

2021 ◽  
Vol 22 (11) ◽  
pp. 6054
Author(s):  
Ioanna Kokkinopoulou ◽  
Paraskevi Moutsatsou
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptors ◽  
Mitochondrial Gene ◽  
Cell Types ◽  
Ros Generation ◽  
Mitochondrial Gene Expression ◽  
Mitochondrial Energy Metabolism ◽  
Bcl2 Family ◽  
Cellular Processes ◽  
Almost All

Mitochondria are membrane organelles present in almost all eukaryotic cells. In addition to their well-known role in energy production, mitochondria regulate central cellular processes, including calcium homeostasis, Reactive Oxygen Species (ROS) generation, cell death, thermogenesis, and biosynthesis of lipids, nucleic acids, and steroid hormones. Glucocorticoids (GCs) regulate the mitochondrially encoded oxidative phosphorylation gene expression and mitochondrial energy metabolism. The identification of Glucocorticoid Response Elements (GREs) in mitochondrial sequences and the detection of Glucocorticoid Receptor (GR) in mitochondria of different cell types gave support to hypothesis that mitochondrial GR directly regulates mitochondrial gene expression. Numerous studies have revealed changes in mitochondrial gene expression alongside with GR import/export in mitochondria, confirming the direct effects of GCs on mitochondrial genome. Further evidence has made clear that mitochondrial GR is involved in mitochondrial function and apoptosis-mediated processes, through interacting or altering the distribution of Bcl2 family members. Even though its exact translocation mechanisms remain unknown, data have shown that GR chaperones (Hsp70/90, Bag-1, FKBP51), the anti-apoptotic protein Bcl-2, the HDAC6- mediated deacetylation and the outer mitochondrial translocation complexes (Tom complexes) co-ordinate GR mitochondrial trafficking. A role of mitochondrial GR in stress and depression as well as in lung and hepatic inflammation has also been demonstrated.

scholarly journals The Quorum Sensing Auto-Inducer 2 (AI-2) Stimulates Nitrogen Fixation and Favors Ethanol Production over Biomass Accumulation in Zymomonas mobilis

2021 ◽  
Vol 22 (11) ◽  
pp. 5628
Author(s):  
Valquíria Campos Alencar ◽  
Juliana de Fátima dos Santos Silva ◽  
Renata Ozelami Vilas Boas ◽  
Vinícius Manganaro Farnézio ◽  
Yara N. L. F. de Maria ◽  
...  
Keyword(s):  
Nitrogen Fixation ◽  
Quorum Sensing ◽  
Ethanol Production ◽  
N2 Fixation ◽  
Energy Demand ◽  
Zymomonas Mobilis ◽  
Biomass Accumulation ◽  
High Energy ◽  
Gram Negative ◽  
Expression Of Genes

Autoinducer 2 (or AI-2) is one of the molecules used by bacteria to trigger the Quorum Sensing (QS) response, which activates expression of genes involved in a series of alternative mechanisms, when cells reach high population densities (including bioluminescence, motility, biofilm formation, stress resistance, and production of public goods, or pathogenicity factors, among others). Contrary to most autoinducers, AI-2 can induce QS responses in both Gram-negative and Gram-positive bacteria, and has been suggested to constitute a trans-specific system of bacterial communication, capable of affecting even bacteria that cannot produce this autoinducer. In this work, we demonstrate that the ethanologenic Gram-negative bacterium Zymomonas mobilis (a non-AI-2 producer) responds to exogenous AI-2 by modulating expression of genes involved in mechanisms typically associated with QS in other bacteria, such as motility, DNA repair, and nitrogen fixation. Interestingly, the metabolism of AI-2-induced Z. mobilis cells seems to favor ethanol production over biomass accumulation, probably as an adaptation to the high-energy demand of N2 fixation. This opens the possibility of employing AI-2 during the industrial production of second-generation ethanol, as a way to boost N2 fixation by these bacteria, which could reduce costs associated with the use of nitrogen-based fertilizers, without compromising ethanol production in industrial plants.

scholarly journals IoT Platform for Energy Sustainability in University Campuses

Sensors ◽  
2021 ◽  
Vol 21 (2) ◽  
pp. 357
Author(s):  
Pedro Moura ◽  
José Ignacio Moreno ◽  
Gregorio López López ◽  
Manuel Alvarez-Campana
Keyword(s):  
Energy Demand ◽  
New Technologies ◽  
Low Cost ◽  
Sustainable Use ◽  
High Energy ◽  
Appropriate Technology ◽  
Monitoring And Control ◽  
Energy Sustainability ◽  
University Campuses ◽  
Iot Platform

University campuses are normally constituted of large buildings responsible for high energy demand, and are also important as demonstration sites for new technologies and systems. This paper presents the results of achieving energy sustainability in a testbed composed of a set of four buildings that constitute the Telecommunications Engineering School of the Universidad Politécnica de Madrid. In the paper, after characterizing the consumption of university buildings for a complete year, different options to achieve more sustainable use of energy are presented, considering the integration of renewable generation sources, namely photovoltaic generation, and monitoring and controlling electricity demand. To ensure the implementation of the desired monitoring and control, an internet of things (IoT) platform based on wireless sensor network (WSN) infrastructure was designed and installed. Such a platform supports a smart system to control the heating, ventilation, and air conditioning (HVAC) and lighting systems in buildings. Furthermore, the paper presents the developed IoT-based platform, as well as the implemented services. As a result, the paper illustrates how providing old existing buildings with the appropriate technology can contribute to the objective of transforming such buildings into nearly zero-energy buildings (nZEB) at a low cost.

scholarly journals High-Fat Diet Leads to Reduced Protein O-GlcNAcylation and Mitochondrial Defects Promoting the Development of Alzheimer’s Disease Signatures

2021 ◽  
Vol 22 (7) ◽  
pp. 3746
Author(s):  
Ilaria Zuliani ◽  
Chiara Lanzillotta ◽  
Antonella Tramutola ◽  
Eugenio Barone ◽  
Marzia Perluigi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
High Fat Diet ◽  
Mitochondrial Activity ◽  
High Fat ◽  
Hexosamine Biosynthetic Pathway ◽  
Neurodegenerative Process ◽  
The Brain

The disturbance of protein O-GlcNAcylation is emerging as a possible link between altered brain metabolism and the progression of neurodegeneration. As observed in brains with Alzheimer’s disease (AD), flaws of the cerebral glucose uptake translate into reduced protein O-GlcNAcylation, which promote the formation of pathological hallmarks. A high-fat diet (HFD) is known to foster metabolic dysregulation and insulin resistance in the brain and such effects have been associated with the reduction of cognitive performances. Remarkably, a significant role in HFD-related cognitive decline might be played by aberrant protein O-GlcNAcylation by triggering the development of AD signature and mitochondrial impairment. Our data support the impairment of total protein O-GlcNAcylation profile both in the brain of mice subjected to a 6-week high-fat-diet (HFD) and in our in vitro transposition on SH-SY5Y cells. The reduction of protein O-GlcNAcylation was associated with the development of insulin resistance, induced by overfeeding (i.e., defective insulin signaling and reduced mitochondrial activity), which promoted the dysregulation of the hexosamine biosynthetic pathway (HBP) flux, through the AMPK-driven reduction of GFAT1 activation. Further, we observed that a HFD induced the selective impairment of O-GlcNAcylated-tau and of O-GlcNAcylated-Complex I subunit NDUFB8, thus resulting in tau toxicity and reduced respiratory chain functionality respectively, highlighting the involvement of this posttranslational modification in the neurodegenerative process.

scholarly journals Microglia in Neurodegenerative Events—An Initiator or a Significant Other?

2021 ◽  
Vol 22 (11) ◽  
pp. 5818
Author(s):  
Gaylia Jean Harry
Keyword(s):  
Neurovascular Unit ◽  
Cell Types ◽  
In Vitro Assays ◽  
Significant Other ◽  
Neurodegenerative Process ◽  
Target Sites ◽  
Systemic Factors ◽  
Injury And Repair ◽  
The Brain

A change in microglia structure, signaling, or function is commonly associated with neurodegeneration. This is evident in the patient population, animal models, and targeted in vitro assays. While there is a clear association, it is not evident that microglia serve as an initiator of neurodegeneration. Rather, the dynamics imply a close interaction between the various cell types and structures in the brain that orchestrate the injury and repair responses. Communication between microglia and neurons contributes to the physiological phenotype of microglia maintaining cells in a surveillance state and allows the cells to respond to events occurring in their environment. Interactions between microglia and astrocytes is not as well characterized, nor are interactions with other members of the neurovascular unit; however, given the influence of systemic factors on neuroinflammation and disease progression, such interactions likely represent significant contributes to any neurodegenerative process. In addition, they offer multiple target sites/processes by which environmental exposures could contribute to neurodegenerative disease. Thus, microglia at least play a role as a significant other with an equal partnership; however, claiming a role as an initiator of neurodegeneration remains somewhat controversial.

scholarly journals Sigma-1 Receptor Promotes Mitochondrial Bioenergetics by Orchestrating ER Ca2+ Leak during Early ER Stress

Metabolites ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 422
Author(s):  
Zhanat Koshenov ◽  
Furkan E. Oflaz ◽  
Martin Hirtl ◽  
Johannes Pilic ◽  
Olaf A. Bachkoenig ◽  
...  
Keyword(s):  
Er Stress ◽  
Energy Demand ◽  
Molecular Mechanisms ◽  
High Energy ◽  
Human Neuroblastoma Cell ◽  
Mitochondrial Bioenergetics ◽  
Dependent Manner ◽  
Human Neuroblastoma ◽  
Sigma 1 Receptor ◽  
Sigma 1

The endoplasmic reticulum (ER) is a complex, multifunctional organelle of eukaryotic cells and responsible for the trafficking and processing of nearly 30% of all human proteins. Any disturbance to these processes can cause ER stress, which initiates an adaptive mechanism called unfolded protein response (UPR) to restore ER functions and homeostasis. Mitochondrial ATP production is necessary to meet the high energy demand of the UPR, while the molecular mechanisms of ER to mitochondria crosstalk under such stress conditions remain mainly enigmatic. Thus, better understanding the regulation of mitochondrial bioenergetics during ER stress is essential to combat many pathologies involving ER stress, the UPR, and mitochondria. This article investigates the role of Sigma-1 Receptor (S1R), an ER chaperone, has in enhancing mitochondrial bioenergetics during early ER stress using human neuroblastoma cell lines. Our results show that inducing ER stress with tunicamycin, a known ER stressor, greatly enhances mitochondrial bioenergetics in a time- and S1R-dependent manner. This is achieved by enhanced ER Ca2+ leak directed towards mitochondria by S1R during the early phase of ER stress. Our data point to the importance of S1R in promoting mitochondrial bioenergetics and maintaining balanced H2O2 metabolism during early ER stress.

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