scholarly journals BC-Box Motif in SOCS6 Induces Differentiation of Epidermal Stem Cells into GABAnergic Neurons

2020 ◽  
Vol 21 (14) ◽  
pp. 4947
Author(s):  
Tetsuya Yoshizumi ◽  
Atsuhiko Kubo ◽  
Hidetoshi Murata ◽  
Masamichi Shinonaga ◽  
Hiroshi Kanno
Keyword(s):  
Stem Cells ◽  
Amino Acid ◽  
Cognitive Function ◽  
Neuronal Differentiation ◽  
Amino Acid Sequences ◽  
Cytokine Signaling ◽  
Epidermal Stem Cells ◽  
Suppressor Of Cytokine Signaling ◽  
Socs Proteins ◽  
The Brain

The BC-box motif in suppressor of cytokine signaling 6 (SOCS6) promotes the neuronal differentiation of somatic stem cells, including epidermal stem cells. SOCS6 protein belongs to the group of SOCS proteins and inhibits cytokine signaling. Here we showed that epidermal stem cells were induced to differentiate into GABAnergic neurons by the intracellular delivery of a peptide composed of the amino-acid sequences encoded by the BC-box motif in SOCS6 protein. The BC-box motif (SLQYLCRFVI) in SOCS6 corresponded to the binding site of elongin BC. GABAnergic differentiation mediated by the BC-box motif in SOCS6 protein was caused by ubiquitination of JAK2 and inhibition of the JAK2-STAT3 pathway. Furthermore, GABAnergic neuron-like cells generated from epidermal stem cells were transplanted into the brain of a rodent ischemic model. Then, we demonstrated that these transplanted cells were GAD positive and that the cognitive function of the ischemic model rodents with the transplanted cells was improved. This study could contribute to not only elucidating the mechanism of GABAnergic neuronal differentiation but also to neuronal regenerative medicine utilizing GABAnergic neurons.

A head-activator binding protein is present in hydra in a soluble and a membrane-anchored form

Development ◽  
1999 ◽  
Vol 126 (18) ◽  
pp. 4077-4086 ◽  
Author(s):  
W. Hampe ◽  
J. Urny ◽  
I. Franke ◽  
S.A. Hoffmeister-Ullerich ◽  
D. Herrmann ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amino Acid ◽  
Transmembrane Domain ◽  
Binding Protein ◽  
Amino Acid Sequences ◽  
Secreted Protein ◽  
Specific Antibodies ◽  
Head Activator ◽  
Carboxy Terminal

The neuropeptide head activator plays an important role for proliferation and determination of stem cells in hydra. By affinity chromatography a 200 kDa head-activator binding protein, HAB, was isolated from the multiheaded mutant of Chlorohydra viridissima. Partial amino acid sequences were used to clone the HAB cDNA which coded for a receptor with a unique alignment of extracellular modules, a transmembrane domain, and a short carboxy-terminal cytoplasmic tail. A mammalian HAB homologue with identical alignment of these modules is expressed early in brain development. Specific antibodies revealed the presence of HAB in hydra as a transmembrane receptor, but also as secreted protein, both capable of binding head activator. Secretion of HAB during regeneration and expression in regions of high determination potential hint at a role for HAB in regulating the concentration and range of action of head activator.

Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice

2016 ◽  
Vol 26 (1) ◽  
Author(s):  
Amira Alkharusi ◽  
Mercedes Mirecki-Garrido ◽  
Zuheng Ma ◽  
Fahad Zadjali ◽  
Amilcar Flores-Morales ◽  
...  
Keyword(s):  
Type I Diabetes ◽  
Janus Kinase ◽  
Cytokine Signaling ◽  
Type I ◽  
Suppressor Of Cytokine Signaling ◽  
Β Cell ◽  
Diabetes In Mice ◽  
Socs Proteins ◽  
Stat Pathway

AbstractDiabetes type 1 is characterized by the failure of beta cells to produce insulin. Suppressor of cytokine signaling (SOCS) proteins are important regulators of the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway. Previous studies have shown that GH can prevent the development of type I diabetes in mice and that SOCS2 deficiency mimics a state of increased GH sensitivity.The elevated sensitivity of SOCS2We show that 6-month-old SOCS2Knockdown of SOCS2 makes mice less sensitive to MLDSTZ. These results are consistent with the proposal that elimination of SOCS2 in pancreatic islets creates a state of β-cell hypersensitivity to GH/PRL that mimics events in pregnancy, and which is protective against MLDSTZ-induced type I diabetes in mice. SOCS2-dependent control of β-cell survival may be of relevance to islet regeneration and survival in transplantation.

scholarly journals Immune-to-brain signaling and central prostaglandin E2 synthesis in fasted rats with altered lipopolysaccharide-induced fever

2008 ◽  
Vol 295 (1) ◽  
pp. R133-R143 ◽  
Author(s):  
Wataru Inoue ◽  
Gokce Somay ◽  
Stephen Poole ◽  
Giamal N. Luheshi
Keyword(s):  
Inflammatory Responses ◽  
Mammalian Species ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Plasma Cytokines ◽  
Thermoregulatory Function ◽  
Underlying Mechanisms ◽  
Fever Response ◽  
The Brain ◽  
Fasted Rats

Acute starvation attenuates the fever response to pathogens in several mammalian species. The underlying mechanisms responsible for this effect are not fully understood but may involve a compromised immune and/or thermoregulatory function, both of which are prerequisites for fever generation. In the present study, we addressed whether the impaired innate immune response contributes to the reported attenuation of the fever response in fasted rats during LPS-induced inflammation. Animals fasted for 48 h exhibited a significant and progressive hypothermia prior to drug treatment. An intraperitoneal injection of LPS (100 μg/kg) resulted in a significantly attenuated fever in the fasted animals compared with the fed counterparts. This attenuation was accompanied by the diminution in the concentration of some [TNF and IL-1 receptor antagonist (RA)] but not all (IL-1β and IL-6) of the plasma cytokines normally elevated in association with the fever response. Nevertheless, fasting had no effect on the LPS-induced inflammatory responses at the level of the brain, as assessed by mRNA expressions of inhibitory factor(I)-κB, suppressor of cytokine signaling (SOCS3), IL-1β, cyclooxygenase (COX)-2, and microsomal PGE synthase (mPGES)-1 in the hypothalamus, as well as by PGE2 elevations in the cerebrospinal fluid. In contrast, fasting significantly attenuated the fever response to central PGE2 injection. These results show that fasting does not alter the febrigenic signaling from the periphery to the brain important for central PGE2 synthesis but does affect thermoregulatory mechanisms downstream of and/or independent of central PGE2 action.

Human Neural Stem Cells Genetically Modified to Express Human Nerve Growth Factor (NGF) Gene Restore Cognition in the Mouse with Ibotenic Acid-Induced Cognitive Dysfunction

2012 ◽  
Vol 21 (11) ◽  
pp. 2487-2496 ◽  
Author(s):  
Hong J. Lee ◽  
In J. Lim ◽  
Seung W. Park ◽  
Yun B. Kim ◽  
Yong Ko ◽  
...  
Keyword(s):  
Stem Cells ◽  
Nerve Growth Factor ◽  
Cognitive Function ◽  
Growth Factor ◽  
Neural Stem Cells ◽  
Cholinergic Neurons ◽  
Ibotenic Acid ◽  
Learning Deficit ◽  
Human Neural Stem Cells ◽  
The Brain

Alzheimer's disease (AD) is characterized by degeneration and loss of neurons and synapses throughout the brain, causing the progressive decline in cognitive function leading to dementia. No effective treatment is currently available. Nerve growth factor (NGF) therapy has been proposed as a potential treatment of preventing degeneration of basal forebrain cholinergic neurons in AD. In a previous study, AD patient's own fibroblasts genetically modified to produce NGF were transplanted directly into the brain and protected cholinergic neurons from degeneration and improved cognitive function in AD patients. In the present study, human neural stem cells (NSCs) are used in place of fibroblasts to deliver NGF in ibotenic acid-induced learning-deficit rats. Intrahippocampal injection of ibotenic acid caused severe neuronal loss, resulting in learning and memory deficit. NGF protein released by F3.NGF human NSCs in culture medium is 10-fold over the control F3 naive NSCs at 1.2 μg/106 cells/day. Overexpression of NGF in F3.NGF cells induced improved survival of NSCs from cytotoxic agents H2O2, Aβ, or ibotenic acid in vitro. Intrahippocampal transplantation of F3.NGF cells was found to express NGF and fully improved the learning and memory function of ibotenic acid-challenged animals. Transplanted F3.NGF cells were found all over the brain and differentiated into neurons and astrocytes. The present study demonstrates that human NSCs overexpressing NGF improve cognitive function of learning-deficit model mice.

Suppressor of cytokine signaling (SOCS) proteins are induced by IL-7 and target surface CD127 protein for degradation in human CD8 T cells

2016 ◽  
Vol 306-307 ◽  
pp. 41-52 ◽  
Author(s):  
Feras M. Ghazawi ◽  
Elliott M. Faller ◽  
Parmvir Parmar ◽  
Abdulkareem El-Salfiti ◽  
Paul A. MacPherson
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Target Surface ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Socs Proteins

Regulation of innate immunity by suppressor of cytokine signaling (SOCS) proteins

Immunobiology ◽  
2008 ◽  
Vol 213 (3-4) ◽  
pp. 225-235 ◽  
Author(s):  
Alexander Dalpke ◽  
Klaus Heeg ◽  
Holger Bartz ◽  
Andrea Baetz
Keyword(s):  
Innate Immunity ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Socs Proteins

scholarly journals Deletion of suppressor of cytokine signaling 3 (SOCS3) in muscle stem cells does not alter muscle regeneration in mice after injury

PLoS ONE ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. e0212880
Author(s):  
Kristy Swiderski ◽  
Marissa K. Caldow ◽  
Timur Naim ◽  
Jennifer Trieu ◽  
Annabel Chee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Muscle Regeneration ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Muscle Stem Cells

scholarly journals The novel gene asb11: a regulator of the size of the neural progenitor compartment

2006 ◽  
Vol 174 (4) ◽  
pp. 581-592 ◽  
Author(s):  
Sander H. Diks ◽  
Robert J. Bink ◽  
Sandra van de Water ◽  
Jos Joore ◽  
Carina van Rooijen ◽  
...  
Keyword(s):  
Neuronal Differentiation ◽  
Relative Increase ◽  
Cytokine Signaling ◽  
The Novel ◽  
Suppressor Of Cytokine Signaling ◽  
Neuronal Progenitor ◽  
Undifferentiated State ◽  
The Central Nervous System ◽  
Progenitor Compartment ◽  
Danio Rerio Embryos

From a differential display designed to isolate genes that are down-regulated upon differentiation of the central nervous system in Danio rerio embryos, we isolated d-asb11 (ankyrin repeat and suppressor of cytokine signaling box–containing protein 11). Knockdown of the d-Asb11 protein altered the expression of neural precursor genes sox2 and sox3 and resulted in an initial relative increase in proneural cell numbers. This was reflected by neurogenin1 expansion followed by premature neuronal differentiation, as demonstrated by HuC labeling and resulting in reduced size of the definitive neuronal compartment. Forced misexpression of d-asb11 was capable of ectopically inducing sox2 while it diminished or entirely abolished neurogenesis. Overexpression of d-Asb11 in both a pluripotent and a neural-committed progenitor cell line resulted in the stimulus-induced inhibition of terminal neuronal differentiation and enhanced proliferation. We conclude that d-Asb11 is a novel regulator of the neuronal progenitor compartment size by maintaining the neural precursors in the proliferating undifferentiated state possibly through the control of SoxB1 transcription factors.

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