scholarly journals Effect of A Standardized Extract of Asparagus Officinalis Stem on HSP 70 Induction and Redox Balance in Bovine Cumulus-Granulosa Cells

2021 ◽  
Author(s):  
Ho Khoi ◽  
Kohei Homma ◽  
Jun Takanari ◽  
Hanako Bai ◽  
Manabu Kawahara ◽  
...  
Keyword(s):  
Heat Shock ◽  
Stress Condition ◽  
Redox Balance ◽  
Asparagus Officinalis ◽  
Hsp70 Expression ◽  
Ros Generation ◽  
Hsp 70 ◽  
Cellular Redox ◽  
Heat Stress Condition ◽  
Hsp70 Induction

Abstract Heat shock protein 70 (HSP70) is a well-known heat shock (HS)-induced protein that acts as an intracellular chaperone to protect cells against stress conditions. Although HS induces HSP70 expression to acquire stress-resistant ability to cells, HS causes toxicity to cells by increasing reactive oxygen species (ROS). Recently, a standardized extract of Asparagus officinalis stem (EAS), produced from the by-product of asparagus, was found to induce HSP70 expression without HS and regulate cellular redox balance in the cells. However, the effect of EAS on the function of reproductive cells remains unknown. In the present study, we investigated the effect of EAS on HSP70 induction and oxidative redox balance in cultured bovine cumulus-granulosa(CG) cells. EAS significantly increased HSP70 expression, whereas no effect was observed in HSP27 and − 90 under non-heat stress condition. EAS decreased ROS generation and DNA damage, and increased glutathione (GSH) synthesis both under non-HS and HS conditions. Moreover, EAS synergistically increased HSP70 and HSF1 expression. EAS also increased progesterone (P4) levels in CG cells. HSP70 inhibitor significantly decreased GSH and increased ROS, as well as decreased HSF1, Nrf2, and Keap1 in the presence of EAS. These results suggest that EAS regulates redox balance through HSP70 in bovine CG cells.

scholarly journals A standardized extract of Asparagus officinalis stem improves HSP70-mediated redox balance and cell functions in bovine cumulus-granulosa cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Khoi Thieu Ho ◽  
Kohei Homma ◽  
Jun Takanari ◽  
Hanako Bai ◽  
Manabu Kawahara ◽  
...  
Keyword(s):  
Cell Function ◽  
Redox Balance ◽  
Asparagus Officinalis ◽  
Hsp70 Expression ◽  
Ros Generation ◽  
Cellular Redox ◽  
Pheochromocytoma Cells ◽  
Cell Functions ◽  
Progesterone Synthesis ◽  
Hsp70 Induction

AbstractHeat shock (HS) protein 70 (HSP70), a well-known HS-induced protein, acts as an intracellular chaperone to protect cells against stress conditions. Although HS induces HSP70 expression to confer stress resistance to cells, HS causes cell toxicity by increasing reactive oxygen species (ROS) levels. Recently, a standardized extract of Asparagus officinalis stem (EAS), produced from the byproduct of asparagus, has been shown to induce HSP70 expression without HS and regulate cellular redox balance in pheochromocytoma cells. However, the effects of EAS on reproductive cell function remain unknown. Here, we investigated the effect of EAS on HSP70 induction and oxidative redox balance in cultured bovine cumulus-granulosa (CG) cells. EAS significantly increased HSP70 expression; however, no effect was observed on HSP27 and HSP90 under non-HS conditions. EAS decreased ROS generation and DNA damage and increased glutathione (GSH) synthesis under both non-HS and HS conditions. Moreover, EAS synergistically increased HSP70 and HSF1 expression and increased progesterone levels in CG cells. Treatment with an HSP70 inhibitor significantly decreased GSH level, increased ROS level, and decreased HSF1, Nrf2, and Keap1 expression in the presence of EAS. Furthermore, EAS significantly increased progesterone synthesis. Thus, EAS improves HSP70-mediated redox balance and cell function in bovine CG cells.

Isolation and Structure Determination of a Heat Shock Protein Inducer, Asparagus-Derived Proline-Containing 3-Alkyldiketopiperazines (Asparaprolines), From a Standardized Extract of Asparagus officinalis Stem

2020 ◽  
Vol 15 (3) ◽  
pp. 1934578X2091468
Author(s):  
Shoichiro Inoue ◽  
Jun Takanari ◽  
Keima Abe ◽  
Ayako Nagayama ◽  
Yukinobu Ikeya ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Spectroscopic Data ◽  
Asparagus Officinalis ◽  
Hsp70 Mrna ◽  
Mrna Induction ◽  
Natural Amino Acids ◽  
First Time ◽  
Hsp70 Induction

ETAS® has been developed from the stems of Asparagus officinalis L. as a functional ingredient for nutraceuticals. ETAS possesses heat shock protein 70 (HSP70) induction activity and may contribute to maintenance and improvement of health. Here, 3 compounds (1, 2, 3) were isolated from ETAS. The structures of 1, 2, and 3 were deduced by HREIMS and NMR spectroscopic data, and the compounds were identified as cyclo(l-Phe-l-Pro), cyclo(l-Tyr-l-Pro), and cyclo(l-Leu-l-Pro), respectively. Each compound contained a diketopiperazine ring derived from proline with an alkyl group at C-3; thus, we termed them asparagus-derived proline-containing 3-alkyldiketopiperazines (Asparaprolines). In an HSP70 mRNA induction assay in HL-60 cells, Asparaprolines significantly enhanced the expression of HSP70 mRNA compared with a control. To our knowledge, these results demonstrate for the first time that proline-containing diketopiperazines derived from natural amino acids exhibit HSP70 mRNA induction activity.

scholarly journals Hsp70 Protects Mitotic Cells against Heat-induced Centrosome Damage and Division Abnormalities

2005 ◽  
Vol 16 (8) ◽  
pp. 3776-3785 ◽  
Author(s):  
Henderika M.J. Hut ◽  
Harm H. Kampinga ◽  
Ody C.M. Sibon
Keyword(s):  
Heat Shock ◽  
Hsp70 Expression ◽  
Defense System ◽  
Hsp 70 ◽  
Cellular Defense ◽  
Proteotoxic Stress ◽  
Antibody Staining ◽  
Abnormal Mitosis ◽  
Interphase Cells ◽  
Mitotic Cells

The effect of heat shock on centrosomes has been mainly studied in interphase cells. Centrosomes play a key role in proper segregation of DNA during mitosis. However, the direct effect and consequences of heat shock on mitotic cells and a possible cellular defense system against proteotoxic stress during mitosis have not been described in detail. Here, we show that mild heat shock, applied during mitosis, causes loss of dynamitin/p50 antibody staining from centrosomes and kinetochores. In addition, it induces division errors in most cells and in the remaining cells progression through mitosis is delayed. Expression of heat shock protein (Hsp)70 protects against most heat-induced division abnormalities. On heat shock, Hsp70 is rapidly recruited to mitotic centrosomes and normal progression through mitosis is observed immediately after release of Hsp70 from centrosomes. In addition, Hsp70 expression coincides with restoration of dynamitin/p50 antibody staining at centrosomes but not at kinetochores. Our data show that during mitosis, centrosomes are particularly affected resulting in abnormal mitosis. Hsp70 is sufficient to protect against most division abnormalities, demonstrating the involvement of Hsp70 in a repair mechanism of heat-damaged mitotic centrosomes.

scholarly journals The rhodanese RhdA helps Azotobacter vinelandii in maintaining cellular redox balance

2010 ◽  
Vol 391 (7) ◽  
Author(s):  
William Remelli ◽  
Angelo Cereda ◽  
Jutta Papenbrock ◽  
Fabio Forlani ◽  
Silvia Pagani
Keyword(s):  
Oxidative Stress ◽  
Stress Condition ◽  
Azotobacter Vinelandii ◽  
Redox Balance ◽  
Cysteine Residue ◽  
Structural Peculiarity ◽  
Cellular Redox ◽  
Catalytic Cysteine ◽  
Transcript Profiles

AbstractThe tandem domain rhodanese-homology protein RhdA ofAzotobacter vinelandiishows an active-site loop structure that confers structural peculiarity in the environment of its catalytic cysteine residue. Thein vivoeffects of the lack of RhdA were investigated using anA. vinelandiimutant strain (MV474) in which therhdAgene was disrupted by deletion. Here, by combining analytical measurements and transcript profiles, we show that deletion of therhdAgene generates an oxidative stress condition to whichA. vinelandiiresponds by activating defensive mechanisms. In conditions of growth in the presence of the superoxide generator phenazine methosulfate, a stressor-dependent induction ofrhdAgene expression was observed, thus highlighting that RhdA is important forA. vinelandiito sustain oxidative stress. The potential of RhdA to buffer general levels of oxidants inA. vinelandiicells via redox reactions involving its cysteine thiol is discussed.

Heat Shock Protein 70 over Expression Is Associated to Imatinib Resistance in Chronic Myelogenous Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2005-2005 ◽  
Author(s):  
Marion Pocaly ◽  
Valérie Lagarde ◽  
Gabriel Etienne ◽  
Jean-Antoine Ribeil ◽  
Marc Bonneu ◽  
...  
Keyword(s):  
Heat Shock ◽  
Cell Line ◽  
Fold Increase ◽  
Hsp70 Expression ◽  
Hsp 70 ◽  
Imatinib Resistance ◽  
Over Expression ◽  
Imatinib Resistant

Abstract Imatinib is an effective therapy for chronic myeloid leukemia (CML), a myeloproliferative syndrome characterised by the expression of the recombinant oncoprotein Bcr-Abl. Imatinib inhibits Bcr-Abl tyrosine kinase activity leading to apoptosis of leukemic cells sparing normal hematopoiesis. Several mechanisms of resistance to imatinib have been identified both in vitro and in vivo: Bcr-Abl mutations, an over-expression of the Bcr-Abl kinase itself or other tyrosine kinase bypass. To identify unknown mechanism, we used an imatinib resistant cell line (K562-R) generated from the erythroblastic cell line K562 (K562-S) (Blood, 2000; 93: 1070–1079) for which all described mechanisms of resistance have been previously invalidated. Previous results from a proteomic study identified some chaperon proteins such as heat shock proteins with an increased expression level in K562-R. One of them, the heat shock protein 70, Hsp70, has a 3 fold increase expression level in K562-R cells, results which have been confirmed by western-blot analysis. To characterise the role of Hsp 70 in imatinib resistance, we inhibit Hsp 70 expression by RNA silencing (siRNA) in K562-R cells and over-express it in K562-S cells. Inhibition of Hsp70 protein expression by siRNA decrease Hsp70 expression rapidly over 90% at day 4 which is associated with a significant reduction of viability (66 ± 6%, n = 5, p < 0.03). Over expression of Hsp 70 in K562-S cells induced a significant increase of resistance to imatinib since the addition of imatinib only increases mortality by 27 ± 5 % in comparison to 52 ± 4 % for K562-S cells (n = 4, p < 0.001). Detection of HSF-1 phosphorylation, the major transcription factor involved in Hsp 70 expression, did not show significant differences between K562-S and K562-R cells although over a 3 fold increase is detected in the mRNA level of Hsp 70 in K562-R cells by quantitative PCR. Furthermore, the comparison of Hsp70 expression in mononuclear cells of 7 CML patients before imatinib treatment and at the relapse time shows that Hsp 70 is increased in imatinib resistant patients suggesting it could also play a role in resistance in vivo. Present study confirmed that over expression of Hsp 70 in the cell line K562-R is involved in the mechanism of imatinib resistance in vitro. Moreover, the correlation between the increase of Hsp 70 in CML patient cells and resistance suggests it could be an interesting marker and potentially a therapeutic target.

The Combination of PEITC (Phenehyl Isothiocyanate) with a Histone Deacetylase Inhibitor (HDACi) Has Synergistic Antileukemia Activity by Overcoming a Redox-Mediated Resistance Pathway.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1739-1739
Author(s):  
Yumin Hu ◽  
Gang Chen ◽  
Yu Jia ◽  
Hui Zhang ◽  
Peng Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Histone Deacetylase ◽  
Cell Lines ◽  
Redox Balance ◽  
Ros Generation ◽  
Combination Effect ◽  
Antioxidant Genes ◽  
Cellular Redox ◽  
Cellular Defense

Abstract Abstract 1739 Poster Board I-765 Introduction Histone deacetylase inhibitors (HDACI) have limited but well established clinical activity in human leukemia. Results of a phase 1 trial of vorinostat in AML indicate that a gene signature composed mainly of antioxidants was associated with clinical resistance to vorinostat (Blood 2008;111:1060-60). This study suggested that generation of reactive oxygen species (ROS) appears to be a mechanism of action of vorinostat whereas increase of antioxidants may correlate with vorinostat resistance. The aims of this study were to further investigate the underlying molecular mechanisms and test the combination effect of vorinostat and redox modulation agents. Methods and results The parental HL60 and the pan-HDACI resistant HL60/LR were used to compare the redox parameters in this pair of cell lines. Real time PCR and western blot analysis demonstrated that a variety of glutathione related antioxidant defense enzymes were substantially increased in HL60/LR compared to its parental HL60, which is consistent with the clinical findings cited above. Most importantly, Nrf2, a master transcription factor that activates the transcription of cellular defense and antioxidant genes was also upregulated in HL60/LR. Confocal microscopy study showed that vorinostat treatment of HL60 cells caused translocation of Nrf2 from cytosol to nucleus. Furthermore, its downstream antioxidant genes including GST (glutathione S- Transferase), GSR (glutathione reductase), GCLC (glutathione synthase) and SOD (superoxide dismutase) were upregulated, demonstrating that the cellular defense against oxidative stress was induced by vorinostat. Overexpression of Nrf2 in HEK293 cells prevented ROS generation induced by vorinostat. Knock-down of Nrf2 by siRNA in colon cancer cell HCT116 caused increase of ROS production and cytotoxicity induced by vorinostat. These findings further demonstrated the role of Nrf2 in protecting cells from oxidative stress caused by vorinostat. We also observed that vorinostat substantially activated a ROS generating enzyme NADPH Oxidase (NOX) in various AML cell lines including HL60, U937 and ML1. Vorinostat induced ROS in both HL60 and the mitochondrial deficient cell line HL60-C6F. This indicates that NOX is a major source of ROS generation induced by vorinostat. As a result, modulation of antioxidant response may potentiate the cytotoxic activity of vorinostat. In order to modulate cellular redox balance and overcome the resistance to vorinostat, PEITC, a compound known to deplete cellular glutathione was used to test its combination effect with vorinostat. We found that a subtoxic concentration of PEITC (1-2.5 uM) substantially potentiated cytotoxicity of vorinostat in a dose-dependent manner in various AML cell lines, as demonstrated by Annexin-PI assay after 48 hrs and MTT assay after 72 hrs. Treatment with subtoxic concentrations of vorinostat (1.5 uM) and PEITC (1-2.5 uM) for 48 hrs also resulted in synergistic cytotoxicity in primary leukemia cells obtained from AML patient samples as demonstrated by Annexin-PI assay. Parallel results were also obtained with other HDACI such as MGCD0103. Conclusions Our study indicates that NADPH Oxidase is likely a major source of ROS generation induced by vorinostat. Nrf2, a master transcription factor and its downstream antioxidant genes, which protect cells from oxidative stress, contributes to leukemia cellular resistance to vorinostat. Modulation of cellular redox balance such as depletion of glutathione by PEITC significantly potentiates the anti-leukemia activity of vorinostat. Our study provides important information for further development of a mechanism-based combination strategy to maximize the potential of vorinostat and other HDACI and provides an alternative mechanism of the anti-leukemia activity of HDACI. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Potential of Natural Propolis Extract Combined with Bovine Bone Graft in Increasing Heat Shock Protein 70 and Osteocalcin on Socket Preservation

2020 ◽  
Vol 14 (01) ◽  
pp. 031-037
Author(s):  
Utari Kresnoadi ◽  
Retno Pudji Rahayu ◽  
Maretaningtias Dwi Ariani ◽  
Soesanto Soesanto
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Bone Graft ◽  
Hsp70 Expression ◽  
Bovine Bone ◽  
Hsp 70 ◽  
Osteoblast Cells ◽  
Socket Preservation ◽  
Propolis Extract ◽  
Significant Difference

Abstract Objective This study aims to combine natural propolis with bovine bone graft (BBG) as a means of extraction socket preservation after 3 and 7 days toward expression of heat shock protein (HSP) 70 and osteocalcin to regenerate bone. Materials and Methods The Cavia cobaya were divided into eight groups, each consisting of seven samples. Their lower left incisors were extracted and induced with PEG, propolis extract, BBG, and a combination of propolis extract BBG. The research subjects were terminated on days 3 and 7 postextraction. Immunohistochemical and histopathological examinations were subsequently performed to observe HSP 70 expression, osteocalcin expression, osteoblasts, and osteoclasts. Statistical Analysis Data obtained were then analyzed with one-way analysis of variance (ANOVA) and Tukey’s honestly significant difference (HSD) tests. Results Both the groups with the combination of propolis extract and BBG on days 3 and 7 were found to present the highest number of HSP70 expression, osteocalcin expression, and osteoblast cells as well as the lowest number of osteoclasts. Conclusion Both the groups with the combination of propolis extract and BBG on days 3 and 7 were found to present the highest number of HSP70 expression, osteocalcin expression, and osteoblast cells as well as the lowest number of osteoclasts.

scholarly journals The SP/NK1R System-Mediated ROS Generation in GBM Cells through Inhibiting Glutaredoxin Protein

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Negeen Mehrabani ◽  
Mohammad Reza Vaezi Kakhki ◽  
Hossein Javid ◽  
Safieh Ebrahimi ◽  
Seyed Isaac Hashemy
Keyword(s):  
Redox Balance ◽  
Ros Generation ◽  
Contributing Factors ◽  
Cellular Redox ◽  
Redox Active ◽  
Resazurin Assay ◽  
Intracellular Ros ◽  
Polymerase Chain ◽  
Neurokinin 1 ◽  
Redox Buffer

Altered redox balance is among the main contributing factors developing glioblastoma multiforme (GBM), a highly aggressive grade IV brain tumor. Neuropeptide substance P (SP) plays a key role in modifying the cellular redox environment by activating the neurokinin-1 receptor (NK1R). In this study, we aimed to investigate the redox-modulating properties of both SP and a commercially available NK1R antagonist, aprepitant in GBM cells. To detect the effect of aprepitant on the viability of U87 glioblastoma cells, resazurin assay was applied. The level of intracellular ROS was assessed using 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) assay. The expression of glutaredoxin, a well-known redox-active protein, was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Concurrently, the activity of glutaredoxin was also analyzed by a commercial kit (ZellBio GmbH). We found that SP increased the intracellular levels of reactive oxygen species (ROS) in U87 GBM cells, and aprepitant remarkably decreased this effect. We also explored the effects of SP/NK1R signaling on the glutaredoxin system as a major cellular redox buffer in GBM cells. SP reduced both expression and enzymatic activity of glutaredoxin, and these effects were significantly decreased by aprepitant. In conclusion, our results suggest a possible involvement of SP/NK1R signaling in GBM pathogenesis through oxidative stress and offering new insight for the application of aprepitant as a redox-modulating strategy in GBM patients.

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