Browse
Submit Data
Databases
API
Help

Dataset Information

7 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neuroprotective effect of heat shock protein 60 on matrine-suppressed microglial activation.

ABSTRACT: Matrine (MT) is the primary active alkaloid separated from members of the Sophora genus. Previous studies have reported that MT has anti-inflammatory effects in the central nervous system (CNS). However, the underlying molecular mechanism of the neuroprotective effect of MT remains unclear, particularly the role of heat shock protein 60 (HSP60). Microglia are macrophages in the CNS that serve an essential role in the innate immune system by producing various proinflammatory and neurotoxic factors. In addition, HSP60 is released by activated microglia causing an autoimmune response. The present study aimed to investigate whether MT could inhibit the activation of microglia via suppressing the HSP60 signaling pathway. The results demonstrated that the expression and release of HSP60 in LPS-activated BV2 microglial cells was significantly decreased by MT treatment. Extracellular HSP60 is a ligand of toll like receptor 4 (TLR-4); thus, it was hypothesized that secreted HSP60 could bind to TLR-4 on microglia and activate the TLR-4 signaling pathway. As expected, western blotting and ELISA results revealed that MT significantly inhibited the LPS-induced increase in TLR-4, myeloid differentiation primary response protein MyD88, caspase-3 and tumor necrosis factor-α. In conclusion, the results of the present study provide a novel direction for the prevention and treatment of neurodegenerative diseases characterized by microglial activation.

SUBMITTER: Zhang R

PROVIDER: S-EPMC5526203 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Detrimental Effect of Fungal 60-kDa Heat Shock Protein on Experimental Paracoccidioides brasiliensis Infection.

Project description:The genus Paracoccidioides comprises species of dimorphic fungi that cause paracoccidioidomycosis (PCM), a systemic disease prevalent in Latin America. Here, we investigated whether administration of native 60-kDa heat shock protein of P. brasiliensis (nPbHsp60) or its recombinant counterpart (rPbHsp60) affected the course of experimental PCM. Mice were subcutaneously injected with nPbHsp60 or rPbHsp60 emulsified in complete's Freund Adjuvant (CFA) at three weeks after intravenous injection of P. brasiliensis yeasts. Infected control mice were injected with CFA or isotonic saline solution alone. Thirty days after the nPbHsp60 or rPbHsp60 administration, mice showed remarkably increased fungal load, tissue inflammation, and granulomas in the lungs, liver, and spleen compared with control mice. Further, rPbHsp60 treatment (i) decreased the known protective effect of CFA against PCM and (ii) increased the concentrations of IL-17, TNF-?, IL-12, IFN-?, IL-4, IL-10, and TGF-? in the lungs. Together, our results indicated that PbHsp60 induced a harmful immune response, exacerbated inflammation, and promoted fungal dissemination. Therefore, we propose that PbHsp60 contributes to the fungal pathogenesis.

| S-EPMC5012565 | biostudies-literature

Heat Shock Protein 60 in Cardiovascular Physiology and Diseases.

Project description:Heat shock protein 60 (HSP60) is a highly conserved protein abundantly expressed in both prokaryotic and eukaryotic cells. In mammals, HSP60 has been primarily considered to reside in the mitochondria, where HSP60 and HSP10 form a complex and facilitate mitochondrial protein folding. However, HSP60 is also observed in the cytoplasm, the plasma membrane, and the extracellular space. HSP60 regulates a broad spectrum of cellular events including protein trafficking, peptide hormone signaling, cell survival, cell proliferation, inflammation, and immunization. In the cardiovascular system, growing evidence indicates that HSP60 could not only play an important role under physiological conditions, but also regulate the initiation and progression of heart failure and atherosclerosis. In this review, we focus on recent progress in understanding the function of HSP60 in cardiomyocytes, endothelial cells, and vascular smooth muscle cells (VSMCs), respectively, and discuss the related signaling pathways that have been found in these cells, so as to illustrate the role of HSP60 in the development of cardiovascular disease.

| S-EPMC7203681 | biostudies-literature

Extracellular heat shock protein 60, cardiac myocytes, and apoptosis.

Project description:Previously, we have found that changes in the location of intracellular heat shock protein (HSP)60 are associated with apoptosis. HSP60 has been reported to be a ligand of toll-like receptor (TLR)-4.We hypothesized that extracellular HSP60 (exHSP60) would mediate apoptosis via TLR4.Adult rat cardiac myocytes were treated with HSP60, either recombinant human or with HSP60 purified from the media of injured rat cardiac myocytes. ExHSP60 induced apoptosis in cardiac myocytes, as detected by increased caspase 3 activity and increased DNA fragmentation. Apoptosis could be reduced by blocking antibodies to TLR4 and by nuclear factor kappaB binding decoys, but not completely inhibited, even though similar treatment blocked lipopolysaccharide-induced apoptosis. Three distinct controls showed no evidence for involvement of a ligand other than exHSP60 in the mediation of apoptosis.This is the first report of HSP60-induced apoptosis via the TLRs. HSP60-mediated activation of TLR4 may be a mechanism of myocyte loss in heart failure, where HSP60 has been detected in the plasma.

| S-EPMC2949276 | biostudies-literature

Modification of tooth development by heat shock protein 60.

Project description:Although several heat shock proteins have been investigated in relation to tooth development, no available information is available about the spatial and temporal expression pattern of heat shock protein 60 (Hsp 60). To characterize Hsp 60 expression in the structures of the developing tooth germ, we used Western blotting, immunohistochemistry and in situ hybridization. Hsp 60 was present in high amounts in the inner and outer enamel epithelia, enamel knot (EK) and stratum intermedium (SI). Hsp 60 also appeared in odontoblasts beginning in the bell stage. To obtain data on the possible effect of Hsp 60 on isolated lower incisors from mice, we performed in vitro culturing. To investigate the effect of exogenous Hsp 60 on the cell cycle during culturing, we used the 5-bromo-2-deoxyuridine (BrdU) incorporation test on dental cells. Exogenously administered Hsp 60 caused bluntness at the apical part of the 16.5-day-old tooth germs, but it did not influence the proliferation rate of dental cells. We identified the expression of Hsp 60 in the developing tooth germ, which was present in high concentrations in the inner and outer enamel epithelia, EK, SI and odontoblasts. High concentration of exogenous Hsp 60 can cause abnormal morphology of the tooth germ, but it did not influence the proliferation rate of the dental cells. Our results suggest that increased levels of Hsp 60 may cause abnormalities in the morphological development of the tooth germ and support the data on the significance of Hsp during the developmental processes.

| S-EPMC4822183 | biostudies-literature

Heat Shock Protein 60 in Hepatocellular Carcinoma: Insights and Perspectives.

Project description:Heat shock protein 60 (HSP60) is a mitochondrial chaperone that is implicated in physiological and pathological processes. For instance, it contributes to protein folding and stability, translocation of mitochondrial proteins, and apoptosis. Variations in the expression levels of HSP60 have been correlated to various diseases and cancers, including hepatocellular carcinoma (HCC). Unlike other HSPs which clearly increase in some cancers, data about HSP60 levels in HCC are controversial and difficult to interpret. In the current review, we summarize and simplify the current knowledge about the role of HSP60 in HCC. In addition, we highlight the possibility of its targeting, using chemical compounds and/or genetic tools for treatment of HCC.

| S-EPMC7174549 | biostudies-literature

Heat shock protein 60 and immune inflammatory responses in atherosclerosis.

Project description:Hallmarks of inflammation in various cardiovascular diseases, notably atherosclerosis, have been observed for a long time. However, evidence for an (auto)antigen-driven process at these sites of inflammation has come forward only recently. Heat shock proteins (HSPs) have been identified as playing either immunologically mediated disease promoting or protective roles. HSP60 has been shown to trigger innate and adaptive immune responses that initiate the earliest still reversible inflammatory stage of atherosclerosis. HSP60 is structurally highly conserved and abundantly expressed by prokaryotic and eukaryotic cells under stressful conditions. Beneficial protective immunity to microbial HSP60 acquired by infection or vaccination and bona fide autoimmunity to biochemically altered autologous HSP60 is present in all humans. In vitro and in vivo experiments have demonstrated that classical atherosclerosis risk factors can act as endothelial stressors that provoke the simultaneous expression of adhesion molecules and of HSP60 in mitochondria, in cytoplasm, and on the cell surface, where it acts as a "danger signal" for cellular and humoral immune reactions. Hence, protective, preexisting anti-HSP60 immunity may have to be "paid for" by harmful (auto)immune cross-reactive attack on arterial endothelial cells maltreated by atherosclerosis risk factors. These experimentally and clinically proven findings are the basis for the autoimmune concept of atherosclerosis.

| S-EPMC3212728 | biostudies-literature

Heat shock protein 60 regulates yolk sac erythropoiesis in mice.

Project description:The yolk sac is the first site of blood-cell production during embryonic development in both murine and human. Heat shock proteins (HSPs), including HSP70 and HSP27, have been shown to play regulatory roles during erythropoiesis. However, it remains unknown whether HSP60, a molecular chaperone that resides mainly in mitochondria, could also regulate early erythropoiesis. In this study, we used Tie2-Cre to deactivate the Hspd1 gene in both hematopoietic and vascular endothelial cells, and found that Tie2-Cre+Hspd1f/f (HSP60CKO) mice were embryonic lethal between the embryonic day 10.5 (E10.5) and E11.5, exhibiting growth retardation, anemia, and vascular defects. Of these, anemia was observed first, independently of vascular and growth phenotypes. Reduced numbers of erythrocytes, as well as an increase in cell apoptosis, were found in the HSP60CKO yolk sac as early as E9.0, indicating that deletion of HSP60 led to abnormality in yolk sac erythropoiesis. Deletion of HSP60 was also able to reduce mitochondrial membrane potential and the expression of the voltage-dependent anion channel (VDAC) in yolk sac erythrocytes. Furthermore, cyclosporine A (CsA), which is a well-recognized modulator in regulating the opening of the mitochondrial permeability transition pore (mPTP) by interacting with Cyclophilin D (CypD), could significantly decrease cell apoptosis and partially restore VDAC expression in mutant yolk sac erythrocytes. Taken together, we demonstrated an essential role of HSP60 in regulating yolk sac cell survival partially via a mPTP-dependent mechanism.

| S-EPMC6786998 | biostudies-literature

Heat shock protein 60 (HSP60) modulates adiponectin signaling by stabilizing adiponectin receptor.

Project description:Adiponectin, an adipokine produced and secreted by adipocytes, is involved in regulating the development and progression of insulin resistance, diabetes, and diabetic complications. Heat shock protein 60 (HSP60) is a molecular chaperone, most commonly presenting in mitochondria and participating in the maintenance of protein homeostasis. Accumulating studies have demonstrated that the elevated circulating HSP60 and the decreased intracellular HSP60 are closely associated with diabetic complications such as diabetic cardiomyopathy. However, the underlying mechanism remains poorly understood. In the present study, we reported that HSP60 interacted directly with adiponectin receptors. Its abundance was positively associated with adiponectin action. Furthermore, HSP60 depletion markedly mitigated the protective impacts of adiponectin on high glucose-induced oxidative stress and cell apoptosis in rat cardiac H9c2 cells. In addition, HSP60 knockdown significantly enhanced proteasome activity leading to the degradation of adiponectin receptor 1. Taken together, we showed for the first time that HSP60 interacted with adiponectin receptors and mediated adiponectin signaling through stabilizing adiponectin receptor. This in vitro study also provides an alternative explanation for mechanism by which adiponectin exerts its action. Video abstract.

| S-EPMC7147001 | biostudies-literature

Heat-shock (Temp43, 30min, 60 min)

Project description:JN54 (wild-type) cells were incubated in YPD medium at 30 degrees C to a logarithmic phase (OD660=1), followed by treatment with mild heat-shock at 43 degrees C for 30 min in pre-warmed (43 degrees C) 100ml of YPD medium using 500 ml Erlenmeyer flask. JN54 (wild-type) cells were incubated in YPD medium at 30 degrees C to a logarithmic phase (OD660=1), followed by treatment with mild heat-shock at 43 degrees C for 60 min in pre-warmed (43 degrees C) 100ml of YPD medium using 500 ml Erlenmeyer flask. Keywords: Stress response

2005-09-21 | GSE3316 | GEO

On the brotherhood of the mitochondrial chaperones mortalin and heat shock protein 60.

Project description:The heat shock chaperones mortalin/mitochondrial heat shock protein 70 (mtHsp70) and Hsp60 are found in multiple subcellular sites and function in the folding and intracellular trafficking of many proteins. The chaperoning activity of these 2 proteins involves different structural and functional mechanisms. In spite of providing an excellent model for an evolutionarily conserved molecular "brotherhood", their individual functions, although overlapping, are nonredundant. As they travel to various locations, both chaperones acquire different binding partners and exert a more divergent involvement in tumorigenesis, cellular senescence, and immunology. An understanding of their functional biology may lead to novel designing and development of therapeutic strategies for cancer and aging.

| S-EPMC1484513 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data