Heat Shock Protein 70.1 (Hsp70.1) Affects Neuronal Cell Fate by Regulating Lysosomal Acid Sphingomyelinase

AbstractA fundamental question in medical genetics is how the genetic background modifies the phenotypic outcome of mutations. We address this question by focusing on the seam cells, which display stem cell properties in the epidermis of Caenorhabditis elegans. We demonstrate that a putative null mutation in the GATA transcription factor egl-18, which is involved in seam cell fate maintenance, is more tolerated in the CB4856 isolate from Hawaii than the lab reference strain N2 from Bristol. We identify multiple quantitative trait loci (QTLs) underlying the difference in phenotype expressivity between the two isolates. These QTLs reveal cryptic genetic variation that reinforces seam cell fate through potentiating Wnt signalling. Within one QTL region, a single amino acid deletion in the heat shock protein HSP-110 in CB4856 is sufficient to modify Wnt signalling and seam cell development, highlighting that natural variation in conserved heat shock proteins can shape phenotype expressivity.

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Identification of proteins differentially expressed by glutamate treatment in cerebral cortex of neonatal rats

Laboratory Animal Research ◽

10.1186/s42826-019-0026-9 ◽

2019 ◽

Vol 35 (1) ◽

Cited By ~ 2

Author(s):

Ju-Bin Kang ◽

Dong-Ju Park ◽

Phil-Ok Koh

Keyword(s):

Cerebral Cortex ◽

Heat Shock ◽

Heat Shock Protein ◽

Cell Damage ◽

Neuronal Cell ◽

Differentially Expressed ◽

Heat Shock Protein 60 ◽

Sprague Dawley ◽

Two Dimensional Gel Electrophoresis ◽

Specific Proteins

AbstractGlutamate leads to neuronal cell damage by generating neurotoxicity during brain development. The objective of this study is to identify proteins that differently expressed by glutamate treatment in neonatal cerebral cortex. Sprague-Dawley rat pups (post-natal day 7) were intraperitoneally injected with vehicle or glutamate (10 mg/kg). Brain tissues were isolated 4 h after drug treatment and fixed for morphological study. Moreover, cerebral cortices were collected for protein study. Two-dimensional gel electrophoresis and mass spectrometry were carried out to identify specific proteins. We observed severe histopathological changes in glutamate-exposed cerebral cortex. We identified various proteins that differentially expressed by glutamate exposure. Identified proteins were thioredoxin, peroxiredoxin 5, ubiquitin carboxy-terminal hydrolase L1, proteasome subunit alpha proteins, isocitrate dehydrogenase, and heat shock protein 60. Heat shock protein 60 was increased in glutamate exposed condition. However, other proteins were decreased in glutamate-treated animals. These proteins are related to anti-oxidant, protein degradation, metabolism, signal transduction, and anti-apoptotic function. Thus, our findings can suggest that glutamate leads to neonatal cerebral cortex damage by regulation of specific proteins that mediated with various functions.

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Cryptic genetic variation in a heat shock protein shapes the expressivity of a mutation affecting stem cell behaviour in C. elegans

10.1101/2020.09.29.318006 ◽

2020 ◽

Author(s):

Sneha L. Koneru ◽

Mark Hintze ◽

Dimitris Katsanos ◽

Michalis Barkoulas

Keyword(s):

Genetic Variation ◽

Stem Cell ◽

Heat Shock ◽

Heat Shock Protein ◽

Cell Fate ◽

Single Amino Acid ◽

Cryptic Genetic Variation ◽

C Elegans ◽

Seam Cell ◽

The Difference

AbstractA fundamental question in medical genetics is how the genetic background modifies the phenotypic outcome of key mutations. We address this question by focusing on the epidermal seam cells, which display stem cell properties in Caenorhabditis elegans. We demonstrate that a null mutation in the GATA transcription factor egl-18, which is involved in seam cell fate maintenance, is more tolerated and thus has lower expressivity in the divergent CB4856 isolate from Hawaii than the lab reference strain N2 from Bristol. We identify multiple quantitative trait loci (QTLs) underlying the difference in mutation expressivity between the two isolates. These QTLs reveal cryptic genetic variation, which acts to reinforce seam cell fate through potentiating Wnt signalling. Within one QTL region, a single amino acid deletion in the heat shock protein HSP-110 in CB4856 lowers egl-18 mutation expressivity. Our work underscores that natural variation in conserved heat shock proteins can shape mutation expressivity.

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Changes of Mitochondrial DNA and Heat Shock Protein Gene Expressions in Gerbil Hippocampus after Transient Forebrain Ischemia

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1993.98 ◽

1993 ◽

Vol 13 (5) ◽

pp. 773-780 ◽

Cited By ~ 41

Author(s):

K. Abe ◽

J. Kawagoe ◽

M. Aoki ◽

K. Kogure

Keyword(s):

Heat Shock ◽

Heat Shock Protein ◽

Nuclear Dna ◽

Early Stage ◽

Succinic Dehydrogenase ◽

Neuronal Cell ◽

Forebrain Ischemia ◽

Gene Expressions ◽

Mt Dna ◽

Transient Forebrain Ischemia

Hippocampal CA1 neurons are the most vulnerable to transient cerebral ischemia. However, the mechanism has not been fully understood. The level of mRNA for cytochrome C oxidase (COX) subunit I (COX-I), which is encoded by mitochondrial (mt) DNA, progressively decreased in the hippocampal CA1 neurons of gerbils from 3 h of reperfusion after 3.5 min of transient forebrain ischemia and completely disappeared at 7 days. The activity of COX protein also showed an early decrease in CA1 cells and was followed by reduction of the level of COX-I DNA after 2 days. However, succinic dehydrogenase, an mt enzyme encoded by nuclear DNA, maintained normal activity until 1 day in the CA1 cells and significantly decreased at 7 days. The mRNA for mt heat shock protein (HSP) 60 began to increase at 3 h in the CA1 cells and was sustained until 1 day. The mRNAs for 72-kDa heat shock protein and 73-kDa heat shock cognate protein, which are located mainly in the cytoplasm, were induced together in the CA1 cells with a peak at 1–2 days. These results suggest that a disturbance of mt DNA expression occurred in the CA1 neurons at the early stage of reperfusion and was aggravated over the course of time. The disturbance could cause progressive failure of energy production of the cells that eventually results in neuronal cell death.

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Up-regulation of miR-122 protects against neuronal cell death in ischemic stroke through the heat shock protein 70-dependent NF-κB pathway by targeting FOXO3

Experimental Cell Research ◽

10.1016/j.yexcr.2018.04.027 ◽

2018 ◽

Vol 369 (1) ◽

pp. 34-42 ◽

Cited By ~ 14

Author(s):

Dong Guo ◽

Ji Ma ◽

Tengfei Li ◽

Lei Yan

Keyword(s):

Cell Death ◽

Ischemic Stroke ◽

Heat Shock ◽

Heat Shock Protein ◽

Heat Shock Protein 70 ◽

Neuronal Cell Death ◽

Neuronal Cell

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MiR-133b-5p regulates the expression of the heat shock protein 70 during rat neuronal cell apoptosis induced by the gp120 V3 loop peptide

Journal of Medical Virology ◽

10.1002/jmv.24355 ◽

2015 ◽

Vol 88 (3) ◽

pp. 437-447 ◽

Cited By ~ 6

Author(s):

Chenglai Xia ◽

Yantao Cai ◽

Yuyi Lin ◽

Ronghua Guan ◽

Guohong Xiao ◽

...

Keyword(s):

Heat Shock ◽

Heat Shock Protein ◽

Cell Apoptosis ◽

Heat Shock Protein 70 ◽

Neuronal Cell ◽

V3 Loop

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Overexpression of inducible 70-kDa heat shock protein in mouse attenuates skeletal muscle damage induced by cryolesioning

AJP Cell Physiology ◽

10.1152/ajpcell.00399.2005 ◽

2006 ◽

Vol 290 (4) ◽

pp. C1128-C1138 ◽

Cited By ~ 59

Author(s):

Elen H. Miyabara ◽

Jody L. Martin ◽

Tina M. Griffin ◽

Anselmo S. Moriscot ◽

Ruben Mestril

Keyword(s):

Skeletal Muscle ◽

Heat Shock ◽

Heat Shock Protein ◽

Muscle Damage ◽

Neuronal Cell ◽

Protective Agent ◽

Wild Type ◽

Cross Sectional ◽

Skeletal Muscle Damage ◽

Neuronal Cell Adhesion Molecule

Heat shock protein expression is elevated upon exposure to a variety of stresses and limits the extent of stress-induced damage. To investigate the putative role of inducible 70-kDa heat shock protein (HSP70) in skeletal muscle damage and regeneration, soleus and tibialis anterior (TA) muscles from HSP70-overexpressing transgenic mice were subjected to cryolesioning and analyzed after 1, 10, and 21 days. Histological analysis showed that the muscles from both HSP70 and wild-type mice treated with radicicol (a HSP inducer) had decreased necrosis after cryolesioning compared with controls. The decrease in muscle fiber cross-sectional area in both soleus and TA muscles in 10 days postlesioning was attenuated in HSP70 mice compared with wild-type mice. Glutathione peroxidase activity was increased 1 day after cryolesioning in both HSP70 and control mice and remained elevated for up to 21 days. Immunodetection of neuronal cell adhesion molecule (a satellite cell marker) and developmental/neonatal MHC were significantly lower in cryolesioned HSP70-overexpressing mice than in cryolesioned controls. These results suggest that HSP70 protects skeletal muscle against injury and radicicol might be useful as a skeletal muscle protective agent.

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