scholarly journals Extrathymic production of thymulin induced by oxidative stress, heat shock, apoptosis, or necrosis

2017 ◽  
Vol 30 (1) ◽  
pp. 58-69 ◽  
Author(s):  
Sergey M Lunin ◽  
Maxim O Khrenov ◽  
Olga V Glushkova ◽  
Elena V Vinogradova ◽  
Valery A Yashin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Weight ◽  
Stress Response ◽  
Heat Shock ◽  
Cell Types ◽  
Cell Nuclei ◽  
Sequence Comparisons ◽  
Blast Search ◽  
Thymic Peptides ◽  
Thymic Peptide

Thymic peptides are immune regulators produced mainly in the thymus. However, thymic peptides such as thymosin-α and thymopoietin have precursors widely expressed outside the thymus, localized in cell nuclei, and involved in vital nuclear functions. In stress-related conditions, they can relocalize. We hypothesized that another thymic peptide, thymulin, could be similarly produced by non-thymic cells during stress and have a precursor therein. Non-thymic cells, including macrophages and fibroblasts, were exposed to oxidative stress, heat, apoptosis, or necrosis. Extracellular thymulin was identified in media of both cell types 2 h after exposure to stress or lethal signals. Therefore, thymulin is released by non-thymic cells. To examine possible thymulin precursors in non-thymic cells, macrophage lysates were analyzed by western blotting. Bands stained with anti-thymulin antibody were detected in two locations, approximately 60 kDa and 10 kDa, which may be a possible precursor and intermediate. All of the exposures except for heat were effective for induction of the 10 kDa protein. BLAST search using thymulin sequence identified SPATS2L, an intranucleolar stress-response protein with molecular weight of 62 kDa, containing thymulin-like sequence. Comparisons of blots stained with anti-thymulin and anti-SPATS2L antibodies indicate that SPATS2L may be a possible candidate for the precursor of thymulin.

scholarly journals c-Met Signaling Protects from Nonalcoholic Steatohepatitis- (NASH-) Induced Fibrosis in Different Liver Cell Types

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Hannah K. Drescher ◽  
Fabienne Schumacher ◽  
Teresa Schenker ◽  
Maike Baues ◽  
Twan Lammers ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Stress Response ◽  
Kupffer Cells ◽  
Liver Cell ◽  
Immune Cells ◽  
Nonalcoholic Steatohepatitis ◽  
Cell Types ◽  
Oxidative Stress Response ◽  
Cell Type

Nonalcoholic steatohepatitis (NASH) is the most common chronic, progressive liver disease in Western countries. The significance of cellular interactions of the HGF/c-Met axis in different liver cell subtypes and its relation to the oxidative stress response remains unclear so far. Hence, the present study is aimed at investigating the role of c-Met and the interaction with the oxidative stress response during NASH development in mice and humans. Conditional c-Met knockout (KO) lines (LysCre for Kupffer cells/macrophages, GFAPCre for α-SMA+ and CK19+ cells and MxCre for bone marrow-derived immune cells) were fed chow and either methionine-choline-deficient diet (MCD) for 4 weeks or high-fat diet (HFD) for 24 weeks. Mice lacking c-Met either in Kupffer cells, α-SMA+ and CK19+ cells, or bone marrow-derived immune cells displayed earlier and faster progressing steatohepatitis during dietary treatments. Severe fatty liver degeneration and histomorphological changes were accompanied by an increased infiltration of immune cells and a significant upregulation of inflammatory cytokine expression reflecting an earlier initiation of steatohepatitis development. In addition, animals with a cell-type-specific deletion of c-Met exhibited a strong generation of reactive oxygen species (ROS) by dihydroethidium (hydroethidine) (DHE) staining showing a significant increase in the oxidative stress response especially in LysCre/c-Metmut and MxCre/c-Metmut animals. All these changes finally lead to earlier and stronger fibrosis progression with strong accumulation of collagen within liver tissue of mice deficient for c-Met in different liver cell types. The HGF/c-Met signaling pathway prevents from steatosis development and has a protective function in the progression to steatohepatitis and fibrosis. It conveys an antifibrotic role independent on which cell type c-Met is missing (Kupffer cells/macrophages, α-SMA+ and CK19+ cells, or bone marrow-derived immune cells). These results highlight a global protective capacity of c-Met in NASH development and progression.

scholarly journals Role of Heat Shock Transcription Factor in Saccharomyces cerevisiae Oxidative Stress Response

2007 ◽  
Vol 6 (8) ◽  
pp. 1373-1379 ◽  
Author(s):  
Ayako Yamamoto ◽  
Junko Ueda ◽  
Noritaka Yamamoto ◽  
Naoya Hashikawa ◽  
Hiroshi Sakurai
Keyword(s):  
Oxidative Stress ◽  
Saccharomyces Cerevisiae ◽  
Transcription Factor ◽  
Stress Response ◽  
Heat Shock ◽  
Superoxide Anion ◽  
Target Genes ◽  
Oxidative Stress Response ◽  
Heat Shock Transcription Factor ◽  
Negative Regulator

ABSTRACT The heat shock transcription factor Hsf1 of the yeast Saccharomyces cerevisiae regulates the transcription of a set of genes that contain heat shock elements (HSEs) in their promoters and function in diverse cellular processes, including protein folding. Here, we show that Hsf1 activates the transcription of various target genes when cells are treated with oxidizing reagents, including the superoxide anion generators menadione and KO2 and the thiol oxidants diamide and 1-chloro-2,4-dinitrobenzene (CDNB). Similar to heat shock, the oxidizing reagents are potent inducers of both efficient HSE binding and extensive phosphorylation of Hsf1. The inducible phosphorylation of Hsf1 is regulated by the intramolecular domain-domain interactions and affects HSE structure-specific transcription. Unlike the heat shock, diamide, or CDNB response, menadione or KO2 activation of Hsf1 is inhibited by cyclic-AMP-dependent protein kinase (PKA) activity, which negatively regulates the activator functions of other transcriptional regulators implicated in the oxidative stress response. These results demonstrate that Hsf1 is a member of the oxidative stress-responsive activators and that PKA is a general negative regulator in the superoxide anion response.

Survival and Metabolic Function of Freshly Isolated Rat Hepatocytes Exposed First to a Heat Shock and Then to an Oxidative Stress

1999 ◽  
Vol 18 (4) ◽  
pp. 239-244
Author(s):  
Isabelle Latour ◽  
Pedro Buc-Calderon
Keyword(s):  
Oxidative Stress ◽  
Heat Shock ◽  
Reduced Glutathione ◽  
Rat Hepatocytes ◽  
Cell Types ◽  
Isolated Rat Hepatocytes ◽  
Tert Butyl Hydroperoxide ◽  
Shock Proteins ◽  
Freshly Isolated Rat Hepatocytes ◽  
Isolated Rat

The formation of heat shock proteins (hsp) leading to thermotolerance has been extensively reported in many cell types. In freshly isolated rat hepatocytes, hsp were synthesized after 60 minutes of incubation at 42°C. Cell survival was not modified by such a treatment, but protein synthesis, secretion of triglycerides as lipoproteins, and the maintenance of both ATP and glycogen levels were significantly impaired. When exposed to an oxidative stress, heat-shocked hepatocytes were not more resistant than cells always kept at 37°C. Conversely, the addition of tert-butyl hydroperoxide (tBOOH) resulted, in general, in an increased lactate dehydrogenase leakage. The metabolism of tBOOH, as estimated by the reduced glutathione (GSH) content and GSH peroxidase activity, was similar in both control and heat-shocked hepatocytes. Despite the synthesis of hsp in rat hepatocytes, the lack of resistance to a subsequent oxidant injury may be due to the metabolic impairment caused by the heat shock.

scholarly journals Deteriorated Stress Response in Stationary-Phase Yeast: Sir2 and Yap1 Are Essential for Hsf1 Activation by Heat Shock and Oxidative Stress, Respectively

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e111505 ◽  
Author(s):  
Inbal Nussbaum ◽  
Esther Weindling ◽  
Ritta Jubran ◽  
Aviv Cohen ◽  
Shoshana Bar-Nun
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Heat Shock ◽  
Stationary Phase ◽  
And Oxidative Stress

scholarly journals Chronic stress induces co-ordinated cortical microcircuit cell type transcriptomic changes consistent with altered information processing

2020 ◽  
Author(s):  
Dwight F. Newton ◽  
Hyunjung Oh ◽  
Rammohan Shukla ◽  
Keith Misquitta ◽  
Corey Fee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Information Processing ◽  
Stress Response ◽  
Cell Function ◽  
Cell Types ◽  
Brain Regions ◽  
Oxidative Stress Response ◽  
Dendritic Morphology ◽  
Mild Stress ◽  
Cell Type

ABSTRACTMajor depressive disorder (MDD) is associated with altered GABAergic and glutamatergic signalling, suggesting altered excitation-inhibition balance (EIB) in cortical mood- and cognition-regulating brain regions. Information processing in cortical microcircuits involves regulation of pyramidal (PYR) cells by Somatostatin-(SST), Parvalbumin-(PV), and Vasoactive intestinal peptide-(VIP) expressing interneurons. Human and rodent studies suggest that impaired PYR-cell dendritic morphology and decreased SST-cell function may mediate altered EIB in MDD. However, knowledge of co-ordinated changes across microcircuit cell types is virtually absent. We thus investigated the co-ordinated transcriptomic effects of UCMS on microcircuit cell types in the medial prefrontal cortex. C57Bl/6 mice, exposed to unpredictable chronic mild stress (UCMS) or control housing for five weeks were assessed for anxiety- and depressive-like behaviours. Microcircuit cell types were laser-microdissected and processed for RNA-sequencing. UCMS-exposed mice displayed predicted elevated behavioural emotionality. Each microcircuit cell type showed a unique transcriptional signature after UCMS. Pre-synaptic functions, oxidative stress response, metabolism, and translational regulation were differentially dysregulated across cell types, whereas nearly all cell types showed down-regulated post-synaptic gene signatures. At the microcircuit level, we observed a shift from distributed transcriptomic co-ordination across cell types in controls towards UCMS-induced increased co-ordination between PYR-, SST- and PV-cells, and a hub-like role for PYR-cells. Lastly, we identified a microcircuit-wide co-expression network enriched in synaptic, bioenergetic, and oxidative stress response genes that correlated with UCMS-induced behaviours. Together, these findings suggest cell-specific deficits, microcircuit-wide synaptic reorganization, and a shift in cortical EIB mediated by increased co-ordinated regulation of PYR-cells by SST- and PV-cells.

scholarly journals Characterization of the stress-inducing effects of homocysteine

1998 ◽  
Vol 332 (1) ◽  
pp. 213-221 ◽  
Author(s):  
P. Andrew OUTINEN ◽  
Sudesh K. SOOD ◽  
Patricia C. Y. LIAW ◽  
Kevin D. SARGE ◽  
Nobuyo MAEDA ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Heat Shock ◽  
Umbilical Vein ◽  
Mrna Levels ◽  
Stress Response Genes ◽  
Umbilical Vein Endothelial Cells ◽  
Shock Proteins

The mechanism by which homocysteine causes endothelial cell (EC) injury and/or dysfunction is not fully understood. To examine the stress-inducing effects of homocysteine on ECs, mRNA differential display and cDNA microarrays were used to evaluate changes in gene expression in cultured human umbilical-vein endothelial cells (HUVEC) exposed to homocysteine. Here we show that homocysteine increases the expression of GRP78 and GADD153, stress-response genes induced by agents or conditions that adversely affect the function of the endoplasmic reticulum (ER). Induction of GRP78 was specific for homocysteine because other thiol-containing amino acids, heat shock or H2O2 did not appreciably increase GRP78 mRNA levels. Homocysteine failed to elicit an oxidative stress response in HUVEC because it had no effect on the expression of heat shock proteins (HSPs) including HSP70, nor did it activate heat shock transcription factor 1. Furthermore homocysteine blocked the H2O2-induced expression of HSP70. In support of our findings in vitro, steady-state mRNA levels of GRP78, but not HSP70, were elevated in the livers of cystathionine β-synthase-deficient mice with hyperhomocysteinaemia. These studies indicate that the activation of stress response genes by homocysteine involves reductive stress leading to altered ER function and is in contrast with that of most other EC perturbants. The observation that homocysteine also decreases the expression of the antioxidant enzymes glutathione peroxidase and natural killer-enhancing factor B suggests that homocysteine could potentially enhance the cytotoxic effect of agents or conditions known to cause oxidative stress.

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