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Glutamine supplementation attenuates intestinal apoptosis by inducing heat shock protein 70 in heatstroke rats

世界急诊医学杂志(英文) 2023年第1期14卷 37-43页

作者： Li-wen Du Bao-qing Xu Kai Xun Fang-qi Zhang Department of Emergency Ningbo No.2 HospitalNingbo 315000China Department of Pathology the 900th Hospital of Joint Logistics Support Force of Chinese PLAFuzhou 350025China Department of Pulmonary and Critical Care Medicine the 987th Hospital of Joint Logistics Support Force of Chinese PLABaoji 721000China

BACKGROUND:heatstroke is the most hazardous heat-related illness and has a high fatality *** investigated whether glutamine supplementation could have a protective effect on heatstroke ***:Twenty-five 12-week-old male Wistar rats(weight 305±16 g)were randomly divided into a control group(n=5),heatstroke(HS)group(n=10),and heatstroke+glutamine(HSG)group(n=10).Seven days before heat exposure,glutamine(0.4 g/[kg·d])was administered to the rats in the HSG group by gavage every *** hours after heat exposure,serum samples were collected to detect white blood cells,coagulation indicators,blood biochemical indicators,and inflammatory cytokines in the *** small intestine tissue was stained to analyze pathological structural changes and ***,immunohistochemistry and Western blotting were used to analyze the expression levels of heat shock protein 70(HSP70).Multiple comparisons were analyzed by using one-way analysis of variance,and the Bonferroni test was conducted for the post hoc ***:After heat exposure,the core temperature of the HS group(40.65±0.31°C)was higher than the criterion of heatstroke,whereas the core temperature of the HSG group(39.45±0.14°C)was lower than the *** supplementation restored the increased white blood cells,coagulation indicators,blood biochemical indicators,and inflammatory cytokines that were induced by heatstroke to normal *** intestinal mucosa was injured,and the structure of tight junctions was damaged in the HS group;however,the structure of intestinal mucosal epithelial cells was stable in the HSG *** supplementation alleviated intestinal apoptosis and up-regulated HSP70 ***:Glutamine supplementation may alleviate intestinal apoptosis by inducing the expression of HSP70 and have a protective effect on heatstroke rats.

关键词： heatstroke Glutamine Core temperature Intestinal apoptosis heat shock protein 70

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heat shock protein 70 antisense oligonucleotide inhibits cell growth and induces apoptosis in human gastric cancer cell line SGC-7901

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World Journal of Gastroenterology 2005年第1期11卷 73-78页

作者： Zhi-GangZhao Wen-LuShen DepartmentofSurgery ShantouUniversityMedicalCollegeShantou515031GuangdongProvinceChina DepartmentofSurgery No.2AffiliatedHospitalShantouUniversityMedicalCollegeShantou515041GuangdongProvinceChina

AIM: heat shock protein (HSP)70 is over-expressed in human gastric cancer and plays an important role in the progression of this cancer. We investigated the effects of antisense HSP70 oligomer on human gastric cancer cell line SGC-7901, and its potential role in gene therapy for this ***: Human gastric cancer cell line SGC-7901 was treated in vitro with various concentrations of antisense HSP70 oligonucleotides at different intervals. Growth inhibition was determined as percentage by trypan blue dye exclusion test. Extracted DNA was electrophoresed on agarose gel, and distribution of cell cycle and kinetics of apoptosis induction were analyzed by propidium iodide DNA incorporation using flow cytometry, which was also used to detect the effects of antisense oligomer pretreatment on the subsequent apoptosis induced by heat shock in SGC-7901 cells. proteins were extracted for simultaneous measurement of HSP70 expression level by SDS-PAGE Western ***: The number of viable cells decreased in a doseand time-dependent manner, and ladder-like patterns of DNA fragments were observed in SGC-7901 cells treated with antisense HSP70 oligomers at a concentration of 10 μmol/L for 48 h or 8 μmol/L for 72 h, which were consistent with inter-nucleosomal DNA fragmentation. Flow cytometric analysis showed a dose- and time-dependent increase in apoptotic rate by HSP70 antisense oligomers. This response was accompanied with a decrease in the percentage of cells in the G1 and S phases of the cell cycle, suggesting inhibition of cell proliferation. In addition, flow cytometry also showed that pretreatment of SGC-7901 cells with HSP70 antisense oligomers enhanced the subsequent apoptosis induced by heat shock treatment. Western blotting demonstrated that HSP70 antisense oligomers inhibited HSP70 expression, which preceded apoptosis, and HSP70 was undetectable at the concentration of 10 μmol/L for 48 h or 8 μmol/L for 72 ***: Antisense HSP70 oligomers can abr

关键词： Stomach cancer heat shock protein 70 Antisense Oligonucleotides Apoptosis Cell proliferation

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heat shock protein 70 Gene Polymorphisms in Han Nationality of China with Chronic Obstructive Pulmonary Diseases

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2004年第1期24卷 28-31页

作者：谢俊刚徐永键张珍祥倪望陈仕新 Department of Respiratory Medicine

In order to investigate whether polymorphism in gene for heat shock protein 70 (HSP70) has any bearing on individual susceptibility to the development of chronic obstructive pulmonary disease(COPD), the geotypes of 88 patients with COPD and 87 healthy smoking control subjects were tested by polymerase chain reaction followed by restriction fragment polymorphism analysis for HSP70 gene. In COPD group, HSP70 1 genotype A/A, A/B and B/B was 59.1 %, 35.2 % and 5.7 %, HSP70 2 genotype A/A, A/B and B/B was 26.1 %, 54.6 % and 19.3 %, and HSP70 hom genotype A/A, A/B and B/B was 70.4 %, 27.3 % and 2.3 % respectively. In the control group, it was 60.9 %, 27.5 % and 3.5 %, 20.7 %, 56.3 % and 23.0 %, and 54.0 %, 42.5 % and 3.5 %, respectively. The frequency of polymorphic genetypes showed no difference between the COPD group and the control group ( P >0.05). It was suggested that geneic polymorphism in HSP70 is not associated with development of COPD in Han nationality of China.

关键词： lung disease, obstructive heat shock protein 70 smoking

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Neuroprotective effect of heat shock protein 70 Inhibition of Tau protein expression

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Neural Regeneration Research 2009年第12期4卷 1104-1109页

作者： Zhaohui He Xiaochuan Sun Feng Li Yong Jiang Haitao Wu Luping Zheng Department of Neurosurgery First Affiliated Hospital of Chongqing Medical University Chongqing 400016 China Department of Neurosurgery Second People's Hospital of Jining City Jining 272049 Shandong Province China Department of Neurosurgery Affiliated Hospital of Luzhou Medical College Luzhou 646000 Sichuan Province China

BACKGROUND： Previous studies have shown that heat shock protein 70 （HSP70） has neuroprotective effects by decreasing phosphorylation of Tau protein, thereby reducing the expression of Tau protein and proper aggregation. OBJECTIVE： To observe and verify expressional changes of HSP70 and Tau in retinal ganglion cells following stretch injury to the right optic nerve in rats, and to determine the effect of heat stress pretreatment on HSP70 and Tau protein expressions. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Neurology Research Institute of the First Affiliated Hospital of Chongqing Medical University from March to June 2006. MATERIALS： Instant SABC immunohistochemistry kit, as well as mouse anti-HSP70 and rabbit anti-Tau polyclonal antibodies, were purchased from Wuhan Boster Bioengineering Limited, China. METHODS： A total of 57 male, Wistar rats were randomly assigned to 4 groups： control （n = 3）; 150-180 g stretch force was induced in the right optic nerves in stretch-only group （n = 18） to establish optic nerve stretch injury model; heat stress was applied to 18 animals in heat-stress treatment group; 18 rats in the heat-stress pretreatment plus stretch group were subjected to identical stretch injury as stretch-only group after 24-hour heat-stress pretreatment. According to sacrifice time, the groups were assigned to 6 subgroups at different time points of 4, 8, and 16 hours, and 1,3, and 5 days, with 3 rats in each subgroup. No treatment was performed in the control group except anesthesia. MAIN OUTCOME MEASURES： Morphological changes of optic nerves and retinal ganglion cells following stretch injury were observed by light microscopy following hematoxylin-eosin staining. HSP70 and Tau protein expression levels were observed in retinal ganglial cells from each group using im munohistochemistry. RESULTS：（1） Compared with the control group, morphological axonal and retinal ganglial cell changes, as wel

关键词： heat stress heat shock protein 70 Tau axonal injury

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Effects of exogenous human leptin on heat shock protein 70 expression in MCF-7 breast cancer cells and breast carcinoma of nude mice xenograft model

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Chinese Medical Journal 2012年第4期125卷 680-686页

作者： Xue Rong-quan Gu Jun-chao Yu Wei Wang Yu Zhang Zhong-tao Ma Xue-mei Capital Med Univ Beijing Friendship Hosp Dept Gen Surg Beijing 100050 Peoples R China Capital Med Univ Beijing Tiantan Hosp Dept Gen Surg Beijing 100050 Peoples R China

Background It is important to identify the multiple sites of leptin activity in obese women with breast *** this study,we examined the effect of exogenous human leptin on heat shock protein 70 （HSP70） expression in MCF-7 human breast cancer cells and in a breast carcinoma xenograft model of nude *** We cultured MCF-7 human breast cancer cells and established nude mice bearing xenograffs of these cells,and randomly divided them into experimental and control *** experimental group was treated with human leptin,while the control group was treated with the same volume of normal saline.A real-time reverse transcriptase-polymerase chain reaction （RT-PCR） assay was developed to quantify the mRNA expression of HSP70 in the MCF-7 human breast cancer cells and in tumor *** blotting analysis was applied to quantify the protein expression of HSP70 in the MCF-7 *** staining was done to assess the positive rate of HSP70 expression in the tumor *** Leptin activated HSP70 in a dose-dependent manner in vitro：leptin upregulated significantly the expression of HSP70 at mRNA and protein levels in MCF-7 human breast cancer cells （P 〈0.001）.There was no significant difference in expression of HSP70 mRNA in the implanted tumors between the leptin-treated group and the control group （P〉0.05）.Immunohistochemical staining revealed no significant difference in tumor HSP70 expression between the leptin-treated group and the control group （P〉0.05）.Conclusions A nude mouse xenograft model can be safely and efficiently treated with human leptin by subcutaneous injections around the ***70 may be target of leptin in breast *** can significantly upregulate the expression of HSP70 in a dose-dependent manner in vitro.

关键词： human leptin breast cancer xenografi model heat shock protein 70

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Influence of Tanshinone lla on heat shock protein 70,Bcl-2 and Bax expression in rats with spinal ischemia/reperfusion injury

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Neural Regeneration Research 2012年第36期7卷 2882-2888页

作者： Li Zhang Weidong Gan Guoyao An School of Traumatology and Orthopedics Fujian University of Traditional Chinese Medicine

Tanshinone lla is an effective monomer component of Danshen, which is a traditional Chinese medicine for activating blood circulation to dissipate blood stasis. Tanshinone Ila can effectively improve brain tissue ischemia/hypoxia injury. The present study established a rat model of spinal cord ischemia/reperfusion injury and intraperitoneally injected Tanshinone lla, 0.5 hour prior to model establishment. Results showed that Tanshinone Ila promoted heat shock protein 70 and Bcl-2 protein expression, but inhibited Bax protein expression in the injured spinal cord after ischemia/reperfusion injury. Furthermore, Nissl staining indicated a reduction in nerve cell apoptosis and fewer pathological lesions in the presence of Tanshinone Ila, compared with positive control Danshen injection.

关键词： Tanshinone Ila Danshen spinal ischemia/reperfusion injury heat shock protein 70 Bcl-2 Bax cellapoptosis Chinese medicine neural regeneration

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Therapeutic efficacy of tumor-derived heat shock protein 70 immunoth erapy combining interleukin-2 on tumor-bearing mice

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Chinese Medical Journal 2003年第2期116卷 288-291页

作者：傅庆国孟凡东沈晓东郭仁宣 The Second General Surgery Department The First Affiliated Hospital of China Medical University The Regional Anatomy Department The First Affiliated Hospital of China Medical University

To investigate the therapeutic efficacy of compound immunotherapy of tumor deri ved heat shock protein 70 (HSP70) and interleukin 2 (IL 2) on tumor bearing m ice, and to provide reference for translating this strategy to human cancer Methods Cell culture, techniques for protein extraction and purification, SDS PAGE, Wes tern blot and capillary electrophoresis for HSP70 detection and purity analysis, and animal experiments were used Mice were treated with HSP70 5 or 10 μg an d IL 2 50 kU, 100 kU or 2 kU (maintaining dosage) at pre viously designated intervals Results Both the mono administration of either HSP70 or IL 2 and the compound immunoth erapy of HSP70 and IL 2 obviously inhibited the growth of the implanted tumor a nd prolonged the life span of the mice to different extents However, long peri ods of tumor free suvival (over 90 days) were demonstrated only in HSP70 10 μg group, HSP70 10 μg IL 2 50 kU group, and HSP70 10 μg IL 2 100 kU group (4 0%, 40%, 60% respectively) On the other hand, none of the mice in the rest gr oups achieved long term survival Statistical significance was apparent in com parison with the groups without long period survival ( P 70 immunotherapy was much more effe ctive than IL 2 alone And in compound immunotherapy, HSP70 was the main factor in delaying or eradicating the tumors The proper combination of HSP70 and IL 2 (10 μg HSP70 and 100 kU IL 2 in this experimental mouse model) clea rly enhanced the immunotherapy efficacy which indicated that the specific immuno therapy as a main part of tumor immunotherapy assisted by cytokine immunotherapy would be a promising strategy in cancer treatment

关键词： neoplasm · heat shock protein 70 · i nterleukin 2

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Effects of Acupuncture at Baihui(DU20) and Zusanli(ST36) on the Expression of heat shock protein 70 and Tumor Necrosis Factor α in the Peripheral Serum of Cerebral Ischemia-Reperfusion-Injured Rats

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Chinese Journal of Integrative Medicine 2014年第5期20卷 369-374页

作者：徐虹孙华陈素辉张亚敏朴元林高扬 Department of Traditional Chinese Medicine Peking Union Medical College HospitalChinese Academy of Medical Sciences Institute of Basic Medical Sciences Peking Union Medical CollegeChinese Academy of Medical Sciences

Objective： To explore the effects of acupuncture on the peripheral serum expression of heat shock protein 70 （HSP70） and tumor necrosis factor a （TNF-α ） in rats with cerebral ischemia-reperfusion injury （CIRI）. Methods： In total, 152 Sprague-Dawley （SD） rats were randomly divided into an operated group and a non-operated group according to a random digits table. The operated group included a sham-operated group, a model group and an acupuncture group, whereas the non-operated group consisted of a normal group. Except for the normal group, each group was further divided into 12, 24, 48, 72, 96, and 144 h time points according to different reperfusion times. Eight rats were assigned in each operated group and in the normal group. The rat model of CIRI was established by the thread occlusion method in the model and acupuncture groups. The acupuncture group was treated with electroacupuncture at Baihui （DU20） and Zusanli （ST36） for the required time after successful operation. Blood was sampled to detect the HSP70 and TNF- o~ content by enzyme linked immunosorbent assay. Results： The expression of HSP70 protein in the peripheral serum of the experimental groups was higher than that in the normal control group. The peak time in both the model and the sham-operated groups was 12 h, and the peak time in the acupuncture group was 24 h. The expression in the acupuncture group declined to a lower level at 72 h and was lower than that in the model and sham-operated groups （P〈0.05）. The peak time for the expression of TNF-α protein in the peripheral serum of both the model and the acupuncture groups was 24 h, but the expression in the acupuncture group was lower than the model group. Additionally, the expression of TNF- o~ in all experimental groups was higher than the normal group （P〈0.05）. Conclusions： Acupuncture at DU20 and ST36 in rats attenuated CIRI, which was associated with a reduction in the expression of HSP70 and TNF-a. These results provide clues to acupuncture＇s

关键词： acupuncture cerebral ischemia-reperfusion injury heat shock protein 70 tumor necrosis factor α

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Radiofrequency ablation,heat shock protein 70 and potential anti-tumor immunity in hepatic and pancreatic cancers:a minireview

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Hepatobiliary & Pancreatic Diseases International 2010年第4期9卷 361-365页

作者： Teng, Li-Song Jin, Ke-Tao Han, Na Cao, Jiang Zhejiang Univ Sch Med Ctr Canc Affiliated Hosp 1 Hangzhou 310003 Zhejiang Peoples R China Zhejiang Univ Sir Run Run Shaw Inst Clin Med Key Lab Biotherapy Zhejiang Prov Hangzhou 310016 Zhejiang Peoples R China

BACKGROUND: Radiofrequency ablation (RFA) is a minimally invasive surgical procedure which has widespread popularity in the treatment of hepatic and pancreatic cancers. Increased evidence indicates that RFA stimulates anti-tumor immunity, possibly through the induction heat shock protein 70 (HSP70) expression. HSP70 has the capacity to affect the immunogenicity of tumor cells, to chaperone antigenic peptides and deliver these into antigen presentation pathways within antigen-presenting cells, and to activate and regulate innate and adaptive immunity, which makes it useful in immunotherapeutic strategies for the treatment of cancers. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1991-2010) on anti-tumor immunity, heat shock protein 70, radiofrequency ablation, hepatic cancer, pancreatic cancer, and other related subjects. RESULTS: RFA has an increasing application in the surgical treatment of hepatic and pancreatic cancers. Increased evidence indicates that RFA can induce the expression of HSP70 which possesses properties that enable it to influence a variety of immunological processes. Tumor-derived HSP70 is regarded as a potent adjuvant facilitating presentation of tumor antigens and induction of anti-tumor immunity. CONCLUSIONS: This review addresses the potential association of RFA, HSP70, and anti-tumor immunity in treatment of hepatic and pancreatic cancers. To establish direct evidence of a potential association of RFA, HSP70, and anti-tumor immunity in hepatic and pancreatic cancers, further investigations should be conducted.

关键词： anti-tumor immunity heat shock protein 70 hepatic cancer pancreatic cancer radiofrequency ablation

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Irradiation facilitates the inhibitory effect of the heat shock protein 90 inhibitor NVP-BEP800 on the proliferation of malignant glioblastoma cells through attenuation of the upregulation of heat shock protein 70

Irradiation facilitates the inhibitory effect of the heat sh...

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2014浙江省神经外科学学术年会

作者： JIANYUE WU WEIMIN WANG QIN SHAO GUOMIN XIAO JUN CHENG YUNPENG YUAN MEI ZHANG Department of Neurosurgery The Affiliated Hospital of Hangzhou Normal University

The present study aimed to investigate the effect of NVPEP800,a novel heat shock protein(Hsp)90 inhibitor of the 2minothieno[2,3]pyrimidine class,in combination with radiation on glioblastoma cells.T98Ghuman glioblas-toma cells were treated with dimethyl sulfoxide(DMSO),NVPEP800,NVPEP800 in combination with Xay irradiation(10Gy,20min),or Xay irradiation only,and cultured for *** viability was measured upon comple-tion of the *** addition,apoptosis was measured and immunoblot analysis was performed to analyze the expression levels of cellular protein inhibitoryκB kinaseβ(IKKβ).The combined treatment with NVPEP800 and Xay irradia-tion resulted in the synergistic destruction of malignant ***,NVPEP800 significantly induced apoptosis in the human glioblastoma *** immunoblot analysis data indicated that NVPEP800 markedly reduced the expression level of IKKβ.The results also revealed that Xay irradiation significantly attenuated the increase in the level of Hsp70 in cells treated with *** elevated levels of Hsp70 are associated with drug resistance induced by Hsp90 inhibitors,the effects of Xay irradiation on Hsp70 levels may be associated with the enhanced effect on cells of the presence of *** results of the current study suggest that irradiation enhances the inhibitory effect of NVPEP800 on the proliferation of malignant glioblastoma cells by downregu-lating the expression level of cellular signaling protein IKKβand attenuating the upregulation of Hsp70 that is induced by NVPEP800.

关键词： heat shock protein 90 inhibitor NVP-BEP800 glioblastoma X-ray irradiation heat shock protein 70

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