scholarly journals Opposed Interplay between IDH1 Mutations and the WNT/β-Catenin Pathway: Added Information for Glioma Classification

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 619
Author(s):  
Alexandre Vallée ◽  
Yves Lecarpentier ◽  
Jean-Noël Vallée
Keyword(s):  
Brain Tumor ◽  
Molecular Mechanisms ◽  
Aerobic Glycolysis ◽  
The Central Nervous System ◽  
Idh1 Mutations ◽  
Definition Of ◽  
Canonical Wnt ◽  
First Time ◽  
Glioma Classification ◽  
Stimulation Of

Gliomas are the main common primary intraparenchymal brain tumor in the central nervous system (CNS), with approximately 7% of the death caused by cancers. In the WHO 2016 classification, molecular dysregulations are part of the definition of particular brain tumor entities for the first time. Nevertheless, the underlying molecular mechanisms remain unclear. Several studies have shown that 75% to 80% of secondary glioblastoma (GBM) showed IDH1 mutations, whereas only 5% of primary GBM have IDH1 mutations. IDH1 mutations lead to better overall survival in gliomas patients. IDH1 mutations are associated with lower stimulation of the HIF-1α a, aerobic glycolysis and angiogenesis. The stimulation of HIF-1α and the process of angiogenesis appears to be activated only when hypoxia occurs in IDH1-mutated gliomas. In contrast, the observed upregula aggressiveness and angiogenesis. Molecular pathways of the malignancy process are involved in early stages of WNT/β-catenin pathway-activated-gliomas, and this even under normoxic conditions. IDH1 mutations lead to decreased activity of the WNT/β-catenin pathway and its enzymatic targets. The opposed interplay between IDH1 mutations and the canonical WNT/β-catenin pathway in gliomas could participate in better understanding of the observed evolution of different tumors and could reinforce the glioma classification.

scholarly journals The Central Nervious System Acts as a Transducer of Stress-Induced Masculinization through Corticotropin-Releasing Hormone B

2018 ◽  
Author(s):  
DC Castañeda Cortés ◽  
LF Arias Padilla ◽  
VS Langlois ◽  
GM Somoza ◽  
JI Fernandino
Keyword(s):  
Molecular Mechanisms ◽  
Sex Reversal ◽  
Environmental Stressors ◽  
Mrna Levels ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Downstream Effector ◽  
The Central Nervous System ◽  
First Time ◽  
The Brain

ABSTRACTExposure to environmental stressors during early development has important implications for rescheduling many cellular and molecular mechanisms. In some fish species, environmental stressors, like high temperatures (HT), cause an increase in cortisol levels. In turn, this mechanism induces sex reversal of genotypic females, overriding genetic factors related to development of the gonad. However, the involvement of the brain in this process is not well clarified. In the present work, we investigated the mRNA levels of corticotropin-releasing hormone b (crhb) and its receptors (crhr1 and crhr2), and found out that they were up-regulated at HT during the critical period of gonadal sex determination in medaka (Oryzias latipes), i.e., when the gonadal primordium is sexually labile. In order to clarify their roles in sex reversal, biallelic mutants for crhr1 and crhr2 were produced by CRISPR/Cas9 technology. Remarkably, biallelic mutant of both loci (crhr1 and crhr2) did not undergo female-to-male sex reversal upon HT exposition, whereas mutants for either crhr1 or crhr2 showed partial, or intersex phenotypes, suggesting that both crh receptors are required for HT-induced masculinization. Inhibition of this process in double crhrs mutants could be successfully rescued through the administration of the downstream effector of the hypothalamic-pituitary interrenal axis, the cortisol. Taken together, these results revealed for the first time the participation of the central nervous system acting as a transducer of masculinization induced by thermal stress.

scholarly journals Stimulation of both aerobic glycolysis and Na+-K+-ATPase activity in skeletal muscle by epinephrine or amylin

1999 ◽  
Vol 277 (1) ◽  
pp. E176-E186 ◽  
Author(s):  
J. Howard James ◽  
Kenneth R. Wagner ◽  
Jy-Kung King ◽  
Rebecca E. Leffler ◽  
Radha Krishna Upputuri ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Atpase Activity ◽  
Extensor Digitorum Longus ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Extensor Digitorum ◽  
Atp Production ◽  
High Concentrations ◽  
First Time ◽  
Stimulation Of

Epinephrine and amylin stimulate glycogenolysis, glycolysis, and Na+-K+-ATPase activity in skeletal muscle. However, it is not known whether these hormones stimulate glycolytic ATP production that is specifically coupled to ATP consumption by the Na+-K+pump. These studies correlated glycolysis with Na+-K+-ATPase activity in resting rat extensor digitorum longus and soleus muscles incubated at 30°C in well-oxygenated medium. Lactate production rose three- to fourfold, and the intracellular Na+-to-K+ratio (Na+/K+) fell with increasing concentrations of epinephrine or amylin. In muscles exposed to epinephrine at high concentrations (5 × 10−7 and 5 × 10−6 M), ouabain significantly inhibited glycolysis by ∼70% in either muscle and inhibited glycogenolysis by ∼40 and ∼75% in extensor digitorum longus and soleus, respectively. In the absence of ouabain, but not in its presence, statistically significant inverse correlations were observed between lactate production and intracellular Na+/K+for each hormone. Epinephrine had no significant effect on oxygen consumption or ATP content in either muscle. These results suggest for the first time that stimulation of glycolysis and glycogenolysis in resting skeletal muscle by epinephrine or amylin is closely linked to stimulation of active Na+-K+transport.

Inflammation induced-PINCH expression leads to actin depolymerization and mitochondrial mislocalization in neurons

2020 ◽  
Author(s):  
Kalimuthusamy Natarajaseenivasan ◽  
Santhanam Shanmughapriya ◽  
Prema Velusamy ◽  
Matthew Sayre ◽  
Alvaro Garcia ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Metabolic Disturbances ◽  
Actin Depolymerization ◽  
Chronic Neuroinflammation ◽  
Impaired Metabolism ◽  
Immunodeficiency Virus ◽  
Mature Neurons ◽  
The Central Nervous System ◽  
First Time

Abstract Diseases and disorders with a chronic neuroinflammatory component are often linked with changes in brain metabolism. Among neurodegenerative disorders, people living with human immunodeficiency virus (HIV) and Alzheimer’s disease (AD) are particularly vulnerable to metabolic disturbances, but mechanistic connections of inflammation, neurodegeneration and bioenergetic deficits in the central nervous system (CNS) are poorly defined. The particularly interesting new cystine histidine-rich protein called PINCH is nearly undetectable in healthy mature neurons, but is robustly expressed in tauopathy-associated neurodegenerative diseases including HIV infection and AD. Although robust PINCH expression has been reported in neurons in the brains of patients with HIV and AD, the molecular mechanisms and cellular consequences of increased PINCH expression in CNS disease was not known. In this context, we have identified the transcription factor responsible for PINCH induction in neuroinflammatory conditions and the effects of increased PINCH expression in neurons. Given that AD and neuroHIV share pathological features including cognitive impairment with chronic neuroinflammation, TNFa plays an important role in neurodegenerative processes. The viral protein Tat, is produced in the brain and is one of the main drivers of neuroinflammation and strongly induces TNFa. Our data show that TNFα-mediated activation of MEF2A via increased cellular calcium induces PINCH. In turn, this leads to disruption of the PINCH-ILK-Parvin ternary complex, cofilin activation by Tesk1 inactivation, and actin depolymerization. Disruption of actin led to perinuclear mislocalization of mitochondria by destabilizing the kinesin-dependent mitochondrial transport machinery resulting in impaired neuronal metabolism. Blocking TNFα-induced PINCH preserves mitochondrial localization and maintains metabolic functioning. These data report for the first time mechanistic and biological consequences of PINCH expression in neurons in the CNS in diseases with a chronic neuroinflammatory component. These findings point to maintenance of PINCH at normal physiological levels as a new therapeutic target for neurodegenerative diseases with impaired metabolism.

scholarly journals Identification, Localization in the Central Nervous System and Novel Myostimulatory Effect of Allatostatins in Tenebrio molitor Beetle

2020 ◽  
Vol 21 (10) ◽  
pp. 3510
Author(s):  
Jan Lubawy ◽  
Paweł Marciniak ◽  
Grzegorz Rosiński
Keyword(s):  
Nervous System ◽  
Contractile Activity ◽  
Tenebrio Molitor ◽  
Corpus Allatum ◽  
Sigmoidal Curve ◽  
The Central Nervous System ◽  
First Time ◽  
Dose Dependent ◽  
The Brain ◽  
Stimulation Of

Allatostatins (ASTs) are pleiotropic insect neuropeptides that are potent myoinhibitors of muscle contractions. In this study, we identified and immunolocalized peptides from the MIP/AST and PISCF/AST families in the nervous system of a model beetle, Tenebrio molitor. Neurons containing MIPs were immunolocalized in the brains of adults and the ventral nerve cords of larvae, pupae and imagines of this species as well as in the retrocerebral complex. PISCFs were immunolocalized in the ventral nerve cord of all stages as well as the brain of the adult beetle. Faint signals were also observed in the corpus allatum but not in the corpus cardiacum. The results allowed us to deduce the sequences of three neuropeptides belonging to MIP/ASTs, Tenmo-MIP4—NWGQFGXWa, Tenmo-MIP5—SKWDNFRGSWa and Tenmo-MIP6—EPAWSNLKGIWa, and one peptide from the PISCF/AST family, QSRYXQCYFNPISCX. Furthermore, we showed for the first time myostimulatory action of endogenous MIP/ASTs. Tenmo-MIP5 caused dose-dependent stimulation of the contractile activity of the beetle oviduct muscles, showing a sigmoidal curve up to 81.20% at the 10−8 M concentration, and the EC50 value for the myostimulatory effect of this peptide was 8.50 × 10−12 M. This is the first report of myostimulatory action of an endogenous myoinhibitory peptide in insect muscles.

Melatonin: Protection of the Intervertebral Disc

2019 ◽  
Vol 2 (3) ◽  
pp. 1-9
Author(s):  
Russel J Reiter ◽  
Sergio Rosales-Corral ◽  
Ramaswamy Sharma
Keyword(s):  
Intervertebral Disc ◽  
Molecular Mechanisms ◽  
Intervertebral Discs ◽  
Lumbar Pain ◽  
Low Back ◽  
Work Time ◽  
Protective Actions ◽  
Aging Populations ◽  
Definition Of ◽  
Endogenous Melatonin

     Low back pain (lumbar pain) due to injury of or damage to intervertebral discs is common in all societies.  The loss of work time as a result of this problem is massive.  Recent research suggests that melatonin may prevent or counteract intervertebral disc damage. This may be especially relevant in aging populations given that endogenous melatonin, in most individuals, dwindles with increasing age. The publications related to melatonin and its protection of the intervertebral disc are reviewed herein, including definition of some molecular mechanisms that account for melatonin’s protective actions. 

TAMM HORSFALL PROTEIN: THE MEN BEHIND THE EPONYM

2019 ◽  
Vol 23 (2) ◽  
pp. 117-119 ◽  
Author(s):  
D. N. Paskalev ◽  
B. T. Galunska ◽  
D. Petkova-Valkova
Keyword(s):  
Viral Replication ◽  
Research Team ◽  
Molecular Mechanisms ◽  
Thick Ascending Limb ◽  
Rockefeller Institute ◽  
The Usa ◽  
Natural Inhibitor ◽  
Simplex Virus ◽  
First Time ◽  
New Protein

Tamm–Horsfall Protein (uromodulin) is named after Igor Tamm and Franc Horsfall Jr who described it for the first time in 1952. It is a glycoprotein, secreted by the cells in the thick ascending limb of the loop of Henle. This protein will perform a number of important pathophysiological functions, including protection against uroinfections, especially caused by E. Сoli, and protection against formation of calcium concernments in the kidney. Igor Tamm (1922-1995) is an outstanding cytologist, virologist and biochemist. He is one of the pioneers in the study of viral replication. He was born in Estonia and died in the USA. In 1964 he was elected for a professorship in Rockefeller Institute for Medical Research, where has been working continuously. Since 1959, he became a head of the virology lab established by his mentor and co-author Franc Horsfall. In the course of studies on the natural inhibitor of viral replication, Tamm and Horsfall isolated and characterized biochemically a new protein named after their names. Franc Lappin Horsfall Jr (1906-1971) was a well-known clinician and virologist with remarkable achievements in internal medicine. He was born and died in the USA. He worked in the Rockefeller Hospital from 1934 to 1960, then in the Center for Cancer Research at the Sloan-Kettering Institute. Here he was a leader of a research team studying the molecular mechanisms of immunity, the effects of chemotherapy with benzimidazole compounds (together with I. Tamm), coxsackie viruses, herpes simplex virus, etc. 

Resolution-Associated Molecular Patterns (RAMPs) as Endogenous Regulators of Glia Functions in Neuroinflammatory Disease

2020 ◽  
Vol 19 (7) ◽  
pp. 483-494
Author(s):  
Tyler J. Wenzel ◽  
Evan Kwong ◽  
Ekta Bajwa ◽  
Andis Klegeris
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Bioactive Lipids ◽  
Prothymosin Α ◽  
Neuroinflammatory Disease ◽  
Cellular Debris ◽  
Αb Crystallin ◽  
Endogenous Regulators ◽  
The Central Nervous System ◽  
Molecular Patterns

: Glial cells, including microglia and astrocytes, facilitate the survival and health of all cells within the Central Nervous System (CNS) by secreting a range of growth factors and contributing to tissue and synaptic remodeling. Microglia and astrocytes can also secrete cytotoxins in response to specific stimuli, such as exogenous Pathogen-Associated Molecular Patterns (PAMPs), or endogenous Damage-Associated Molecular Patterns (DAMPs). Excessive cytotoxic secretions can induce the death of neurons and contribute to the progression of neurodegenerative disorders, such as Alzheimer’s disease (AD). The transition between various activation states of glia, which include beneficial and detrimental modes, is regulated by endogenous molecules that include DAMPs, cytokines, neurotransmitters, and bioactive lipids, as well as a diverse group of mediators sometimes collectively referred to as Resolution-Associated Molecular Patterns (RAMPs). RAMPs are released by damaged or dying CNS cells into the extracellular space where they can induce signals in autocrine and paracrine fashions by interacting with glial cell receptors. While the complete range of their effects on glia has not been described yet, it is believed that their overall function is to inhibit adverse CNS inflammatory responses, facilitate tissue remodeling and cellular debris removal. This article summarizes the available evidence implicating the following RAMPs in CNS physiological processes and neurodegenerative diseases: cardiolipin (CL), prothymosin α (ProTα), binding immunoglobulin protein (BiP), heat shock protein (HSP) 10, HSP 27, and αB-crystallin. Studies on the molecular mechanisms engaged by RAMPs could identify novel glial targets for development of therapeutic agents that effectively slow down neuroinflammatory disorders including AD.

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