• The Korean Journal of Physiology and Pharmacology
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• 제28권4호
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• pp.379-387
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• 2024

Breast cancer (BC) is most commonly diagnosed worldwide. Liquiritigenin is a flavonoid found in various species of the Glycyrrhiza genus, showing anti-tumor activity. This article was to explore the influences of liquiritigenin on the biological behaviors of BC cells and its underlying mechanism. BC cells were treated with liquiritigenin alone or transfected with oe-HSP90 before liquiritigenin treatment. RT-qPCR and Western blotting were employed to examine the levels of HSP90, Snail, E-cadherin, HSC70, and LAMP-2A. Cell viability, proliferation, migration, and invasion were evaluated by performing MTT, colony formation, scratch, and Transwell assays, respectively. Liquiritigenin treatment reduced HSP90 and Snail levels and enhanced E-cadherin expression as well as inhibiting the proliferation, migration, and invasion of BC cells. Moreover, liquiritigenin treatment decreased the expression of HSC70 and LAMP-2A, proteins related to chaperone-mediated autophagy (CMA). HSP90 overexpression promoted the CMA, invasion, and migration of BC cells under liquiritigenin treatment. Liquiritigenin inhibits HSP90-mediated CMA, thereby suppressing BC cell growth.

• 한국전문물리치료학회지
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• 제13권3호
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• pp.57-66
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• 2006

Ischemic stroke results from a transient or permanent reduction in cerebral blood flow that is restricted to the territory of a major brain artery. Thus, this study was performed to examine (1) the effects of swimming exercise on the improvement of muscle atrophy, and (2) exercise and HSP 70 expression in an ischemic stroke model induced by middle cerebral artery occlusion. The results of this study were as follows: One week after ischemic stroke was induced, changes appeared in the muscle weight of the gastrocnemius muscle due to muscle atrophy in the affected side. Group II showed statistically significant difference from group III eight weeks after ischemic stroke was induced. (p<.05). One week and eight weeks after ischemic stroke was induced there was significant decrease in the relative muscle weight of the gastrocnemius muscle in each group except Group IV, while there was statistically significant increase in group II eight weeks after ischemic stroke was induced, compared to group III (p<.05). For neurologic exercise behavior tests, Group II generally had the highest score, compared to other groups. In immunohistochemical observations, Group II showed a decrease in HSP 70. The above results suggest that swimming exercise improved muscle atrophy, changed the HSP 70 expression of ischemic stroke in rats, and contributed to the improvement of exercise function.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6011-6016
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• 2012

Introduction: Epidemiological studies suggest a protective role for ${\beta}$-carotene with several malignancies. Esophageal adenocarcinoma frequently arises from Barrett's esophagus (BE). We postulated that ${\beta}$-carotene therapy maybe protective in BE. Materials and Method: We conducted a prospective study in which 25 mg of ${\beta}$-carotene was administered daily for six-months to six patients. Each patient underwent upper endoscopy before and after therapy and multiple mucosal biopsies were obtained. Additionally, patients completed a gastroesophageal reflux disease (GERD) symptoms questionnaire before and after therapy and severity score was calculated. To study the effect of ${\beta}$-carotene at molecular level, tissue extracts of the esophageal mucosal biopsy were subjected to assessment of heat-shock protein 70 (HSP70). Results: A significant (p<0.05) reduction in mean GERD symptoms severity score from $7.0{\pm}2.4$ to $2.7{\pm}1.7$ following ${\beta}$-carotene therapy was noted. Measurement of Barrett's segment also revealed a significant reduction in mean length after therapy. In fact, two patients had complete disappearance of intestinal metaplasia. Furthermore, marked enhancement of HSP70 expression was demonstrated in biopsy specimens from Barrett's epithelium in four cases that were tested. Conclusions: Long-term ${\beta}$-carotene therapy realizes amelioration of GERD symptoms along with restitution of the histological and molecular changes in esophageal mucosa of patients with BE, associated with concurrent increase in mucosal HSP70 expression.

• 생명과학회지
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• 제28권10호
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• pp.1212-1219
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• 2018

열 충격 단백질인 heat shock protein 90 (Hsp90)은 종양 형성 과정에서 중요한 역할을 하고 있으며, 이에 따라 1세대 및 2세대 Hsp90저해제들이 개발되어, 다양한 암에서의 항암 효과가 보고되어 있다. 2세대 Hsp90저해제로 개발된 BIIB021는 1세대 Hsp90저해제인 17-allylamino-17-demethoxygeldanamycin (17-AAG)에 내성을 나타내는 항암제 다제내성(MDR) 암세포에 감수성을 가진다고 알려져 있지만, 본 연구에서 BIIB021에 내성인 MDR세포로서, MCF7-MDR 및 HeyA8-MDR세포가 해당됨을 밝혔다. BIIB021 감수성을 증강시키는 물질로 비스테로이드성 항염증약물(NSAID)인 dimethyl-celecoxib (DMC)의 BIIB021의 효과 증강 활성을 BIIB021-내성 및 -감수성 MDR 세포에서 확인하였다. MDR세포에 NSAID와 BIIB021의 병합 처리한 경우, NSAID의 자가분해(autophagy) 유도 활성에 의해 MDR세포에서 과잉 발현하는 변이형 mutant p53 (mutp53)을 분해할 뿐만 아니라 BIIB021 처리로 유도되는 Hsp70 발현을 억제하므로써, 암세포의 BIIB021 내성을 극복할 수 있는 활성을 나타내었다. 또한 NSAID 물질인 sulindac sulfate 및 FDA 승인 약물인 niclosamide 도 자가분해 유도 활성으로 Hsp90의 타켓 단백질 인 mutp53 및 c-Myc의 분해를 유도하므로서, 17-AAG 효과를 증강시켰다. 그러므로 본 연구에서는 새로운 BIIB021에 대한 효과 증강 및 내성 극복 물질로서, NSAIDs 및 niclosamide를 발굴하였으며, 이들 물질의 자가분해 경로 활성화에 의하여, BIIB021 효과를 극대화 시킴을 밝혔다.

• 한국수정란이식학회지
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• 제20권3호
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• pp.289-295
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• 2005

본 연구는 돼지에서 스트레스 관련 HSP70 유전자의 다형성과 IVF 수정란의 배발달간의 관련성을 조사하기 위하여 수행되었으며 그 결과는 다음과 같다. HSP70-K1, -K3 및 -K4의 PCR 산물로부터 SSCP 다형성은 각각 다르게 확인되었다. 체외수정란의 분할율 시험에서 HSP70 K1-AA($73.1\%$) 및 K1-AB($62.3\%$) 난할율은 HSP70 K1-BB($49.3\%$)보다 유의적으로 높게 나타났다(p<0.05). 또한 HSP70 K3-AA($72.4\%$) and K3-AB($62.2\%$)형도 HSP70 K3-BB($49.1\%$)형보다 유의적으로 높았다(p<0.05). 돼지품종들과 정자의 HSP70 유전자형에 따른 2-cell 단계까지의 체외수정란 배발달은 유의적 차이를 보였다. Landrace(28.8)와 Duroc(29.8)에서 2세포기까지 발달된 수정란의 수는 Yo.kshire(10.9) 보다 유의적으로 높았다(p<0.05). 또한 HSP70 K4-AB(29.6)형의 2세포기 단계까지의 배발달 수정란 수는 HSP70 K4-AA(10.6)형보다 유의적으로 높았다(p<0.05). 그러나 돼지 품종 및 HSP70 유전자형에 따른 배반포기까지 수정란 배발달 정도는 유의적 차이는 없었다. 이러한 결과들은 돼지 체외수정란의 초기 배발달은 HSP70 유전자형과 품종에 따라서 영향을 받는 것으로 확인되었다.

• 한국잠사곤충학회지
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• 제39권1호
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• pp.36-43
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• 1997

In order to express the FLP recombinase in B. mori cultured cell line, BmN-4, transient expression system using a heat shock protein gene (hsp70) promoter of Dorosophilla melnogaster was constructed. This vector was designated as pHsSV. Activity strength of the hsp70 promoter was compared with that of immediate early gene (IE-1) and polyhedrin gene of BmNPV employing the E. coli $\beta$-galactosidase gene as a reporter gene. The result showed that the pHs $\beta$-gal plasmid vector expressed the $\beta$-galactosidase at 2nd and 3rd day after the transfer of plasmid DNA into BmN-4 cells, which was similar to that of pIE1 $\beta$-gal vector, but different from that of a recombinant virus, vBm $\beta$-gal. For the construction of FLP recombinase transient expression vector, the FLP recombinase gene was cloned by polymerase chain reaction technique. To express the FLP recombinase, this gene was inserted into pHsSV plasmid vector, under the control of the hsp70 promotor, and tranfected in BmN-4 cells. The expressed FLP recombinase was estimated at 44kDa on a 12.5% SDS-PAGE.

• 생명과학회지
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• 제20권4호
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• pp.555-560
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• 2010

이 연구는 Hsp70.1 유전자가 결핍된 생쥐를 이용하여 운동전처치에 따른 신장허혈재관류손상에서 혈청 크레아틴, 신장에서 CuSOD와 MnSOD의 발현변화를 관찰하는데 그 목적을 두고 있다. 실험동물은 c57/BL6 계 수컷(wild type: WT)과 Hsp70.1 knockout (KO) 생쥐를 정상대조군(n=8), 운동군(n=8), 허혈운동군(n=8) 및 허혈군(n=8)의 4군으로 분류하여 이용하였다. 실험종료 후 마취를 한 후 혈청 creatinine을 분석하기 위해서 신장에서 혈액을 추출하였고, 신장을 적출하여 western blot 으로 eCuSOD와 MnSOD 발현변화를 비교하였다. KO 허혈군에서의 CuSOD, MnSOD는 다른 군에 비해 유의하게 낮게(p<0.001, p<0.05) 발현하였으며, creatinine은 높은(p<0.001)농도로 나타났다. 반면 WT에서는 유의한 변화가 나타나지 않았다. 흥미롭게도 KO허혈운동군에서의 CuSOD, MnSOD는 허혈군보다 뚜렷하게 증가하였으며, creatinine은 허혈군에 비해 현저히 감소(p<0.01)하였다. 이상의 결과를 종합하면 Hsp70은 신장허혈재관류손상에 직접적인 관련이 있음을 추정할 수 있다. 따라서 운동전 처치는 허혈성신장기능저하에 예방할 수 있다고 생각된다.

• Asian-Australasian Journal of Animal Sciences
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• 제19권2호
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• pp.280-285
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• 2006

The current study was conducted to investigate the relationship between stress related gene and meat quality in pigs. A total number of 212 three-way cross bred (Landrace-$Yorkshire{\times}Duroc$) and 38 Duroc were sampled from the Korean pig industry to determine genotype frequency of porcine stress syndrome (PSS) and heat shock protein 70 kDa (HSP70) genes and their relationship with carcass traits and longissimus meat quality. Screen of HSP70 was performed by the single strand conformation polymorphism (SSCP) technique. Based on the analysis of restriction fragment length polymorphism (RFLP) in ryanodine receptor 1 (RYR1) gene, genetic disorder of PSS was related to a mutation at $18,168^{th}$ (C to T) of exon 17. There was no significant difference in ultimate meat pH and backfat thickness between HSP70 K1-AA type and -BB type in pure Duroc breed. In Landrace-$Yorkshire{\times}Duroc$ (L-$Y{\times}D$) cross bred pig, our results indicated that HSP70 derivate type in Duroc had a limited effect on backfat thickness, but L-$Y{\times}D$ type had a noticeable linkage with HSP70 K1-AA and K3-AB. This tendency was also observed in hot carcass weight where HSP70 K1-AA and K3-AB resulted in heavier weight with 86.3 kg compared to HSP70 K1-AB and K3-BB of 74.3 kg. Results imply that stress related HSP70 genotype has a potential association with backfat thickness and carcass weight.

• Asian-Australasian Journal of Animal Sciences
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• 제27권5호
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• pp.749-756
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• 2014

The present study was carried out to investigate the effects of dietary antioxidants on pro-inflammatory cytokines, heat shock protein (HSP) and antioxidant status in broiler chicks under summer conditions. A total of 162, 3-d-old broiler chicks were randomly assigned to a basal diet (CON) and the basal diet supplemented with vitamin C (200 mg/kg diet, VCD) or vitamin E (100 mg/kg, VED) until 35 day of age. All birds were exposed to summer diurnal heat stress at average daily fluctuations of temperature between $32^{\circ}C$ to $34^{\circ}C$ at day to $27^{\circ}C$ to $29^{\circ}C$ at night for the entire feeding periods. There was no significant difference in body weight, feed to gain ratio and the relative organ weight except the thymus in response to dietary vitamin C or E supplementation. However, the mRNA expression of interleukin (IL)-$1{\beta}$, IL-6, interferon (IFN)-${\gamma}$, Toll like receptor (TLR)-4 and HSP70 in the liver of birds fed diet containing vitamin C significantly (p<0.05) decreased compared with those in birds fed basal diet. Dietary vitamin E also showed a significant (p<0.05) decrease in the mRNA expression of IL-6 and HSP70 compared with a basal diet. Total antioxidant status (TAS) in serum of birds fed vitamin C supplemented diet was significantly (p<0.05) higher with than that in birds a basal diet. Lipid peroxidation in serum and liver resulted in a significant (p<0.05) decrease in response to dietary vitamin C or E supplementation. In conclusion, dietary supplementation with antioxidant vitamins, especially vitamin C resulted in a significant decrease in the mRNA expression of pro-inflammatory cytokines and HSP70, and higher antioxidant parameters than that of birds on the basal diet under summer conditions.

• Clinical and Experimental Reproductive Medicine
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• 제26권1호
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• pp.103-109
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• 1999

Objective: Heat shock protein 70-2 (Hsp70-2) gene knockout mice are found to have premeiotic arrest at the primary spermatocyte stage with a complete absence of spermatids and spermatozoa. This observation led to the hypothesis that hspA2 may be disrupted in human testes with abnormal spermatogenesis. To test this hypothesis, we studied the mRNA expression of hspA2 in infertile men with azoospermia. Design: The mRNA expression were analyzed by competitive RT-PCR among testes with normal spermatogenesis, pachytene spermatocyte arrest, and sertoli-cell only syndrome. Materials and methods: Testicular biopsy was performed in men with azoospermia (n=15). Specimens were subdivided into three groups: (group 1) normal spermatogenesis (n=5), (group 2) spermatocyte arrest (n=5), (group 3) Sertoli-cell only syndrome (n=5). Total RNA was extracted by Trizol reagent. Total extracted RNA was reverse transcribed into cDNA and amplified by PCR using specific primers for hspA2 target cDNAs. A competitive cDNA fragment was constructed by deleting a defined fragment from the target cDNA sequence, and then coamplified with the target cDNA for competitive PCR. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene was used as an internal control. Results: On Competitive RT-PCR analyses for hspA2 mRNA, significant amount of hspA2 expression was observed in group 1, whereas a constitutively low level of hspA2 was expressed in groups 2 and 3. Conclusion(s): The study demonstrates that the hspA2 gene expression is down-regulated in human testes with abnormal spermatogenesis, which in turn suggests that hspA2 gene may play a specific role during meiosis in human testes.