• BMB Reports
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• 제32권2호
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• pp.112-118
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• 1999

The presence of hypoxic cells in solid tumors has long been considered a problem in cancer treatment such as in radiation therapy or treatment with some anticancer drugs. It has been suggested that hypoxic cells are involved in the development of a more aggressive phenotype and contribute to metastasis. In this study, as an attempt to understand how tumor cells adapt to hypoxic stress, we investigated the regulation of the hypoxia-induced expression of proteins that control essential processes of tumor cell survival and angiogenesis. We first examined whether hypoxia induces stress protein gene expression of murine solid tumor RIF cells. We also examined hypoxia-induced changes in angiogenic gene expression in these cells. Finally, we investigated the association of the elevated levels of stress proteins with the regulation of hypoxia-induced angiogenic gene expression. Results demonstrated that hypoxia induced the expression of the erythropoietin (EPO) gene and at least two major members of stress proteins, heat shock protein 70 (HSP70) and 25 (HSP25) in RIF tumor cells. Evidence that the expression of EPO gene was greatly potentiated in TR cells suggested that the elevated levels of HSPs may play an important role in the regulation of the hypoxia-induced EPO gene expression. One of the RIF variant cell lines, TR, displays elevated levels of HSPs constitutively. Taken together, our results suggest that a hypoxic tumor microenvironment may promote the survival and malignant progression of the tumor cells by temporarily increasing the level of stress proteins and expressing angiogenic genes. We suspect that stress proteins may be associated with the increase of the angiogenic potential of tumor cells under hypoxia.

• Journal of Animal Science and Technology
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• 제64권1호
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• pp.110-122
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• 2022

The reduction of milk yield caused by heat stress in summer is the main condition restricting the economic benefits of dairy farms. To examine the impact of hyperthermia on bovine mammary epithelial (MAC-T) cells, we incubated the MAC-T cells at thermal-neutral (37℃, CON group) and hyperthermic (42℃, HS group) temperatures for 6 h. Subsequently, the cell viability and apoptotic rate of MAC-T cells, apoptosis-related genes expression, casein and amino acid transporter genes, and the expression of the apoptosis-related proteins were examined. Compared with the CON group, hyperthermia significantly decreased the cell viability (p < 0.05) and elevated the apoptotic rate (p < 0.05) of MAC-T cells. Moreover, the expression of heat shock protein (HSP)70, HSP90B1, Bcl-2-associated X protein (BAX), Caspase-9, and Caspase-3 genes was upregulated (p < 0.05). The expression of HSP70 and BAX (pro-apoptotic) proteins was upregulated (p < 0.05) while that of B-cell lymphoma (BCL)2 (antiapoptotic) protein was downregulated (p < 0.05) by hyperthermia. Decreased mRNA expression of mechanistic target of rapamycin (mTOR) signaling pathway-related genes, amino acid transporter genes (SLC7A5, SLC38A3, SLC38A2, and SLC38A9), and casein genes (CSNS1, CSN2, and CSN3) was found in the heat stress (HS) group (p < 0.05) in contrast with the CON group. These findings illustrated that hyperthermia promoted cell apoptosis and reduced the transport of amino acids into cells, which inhibited the milk proteins synthesis in MAC-T cells.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제36권5호
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• pp.346-352
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• 2010

Introduction: Heat shock protein70 (HSP70) is a highly conserved family of proteins produced after a variety of stresses. Many studies reported that the overexpression of HSP70 can improve the prognosis of the patients with sepsis through a reduction of the nitric oxide concentration. However, these results only revealed the effect of HSP70 and nitric oxide. No studies have examined the relationship between HSP70 and nitric oxide. The aim of this study was to evaluate the effect of the overexpression of HSP70 on the expression of inducible nitric oxide synthase and the nitric oxide concentration. In addition, the mechanism of the relationship of HSP70 and inducible nitric oxide synthase (iNOS) in sepsis was examined. Materials and Methods: The experiments were performed on male sprague-dawley rats. Sepsis was induced by a cecal ligation and puncture (CLP). Glutamine (GLN) or saline was administered 1 hour after the initiation of sepsis. Serum and lung tissues were acquired from the rats 12 hours or 24 hours after the initiation of sepsis. The nitric oxide concentration, the expression of HSP70 in lung, and the gene expression of iNOS in lung were analyzed. The three groups, sham operation, CLP and CLP+GLN, were compared. Results: Compared to the other groups, in CLP+GLN, GLN administered after the initiation of sepsis enhanced the expression of HSP70 in the lung at 12 hours ($47.19{\pm}10.04$ vs. $33.22{\pm}8.28$, P=0.025) and 24 hours ($47.06{\pm}10.60$ vs. $31.90{\pm}4.83$, P=0.004). In CLP+GLN, GLN attenuated the expression of iNOS messenger RNA (mRNA) in the lung at 12 hours ($5,513.73{\pm}1,051.60$ vs. $4,167.17{\pm}951.59$, P=0.025) and 24 hours ($18,740.27{\pm}8,241.20$ vs. $9,437.65{\pm}2,521.07$, P=0.016), and reduced the concentration of nitric oxide in the serum at 12 hours ($0.86{\pm}0.48$ vs. $3.82{\pm}2.53$, P=0.016) and 24 hours ($0.39{\pm}0.25$ vs. $1.85{\pm}1.70$, P=0.025). Conclusion: The overexpression of HSP70 induced by the administration of GLN in sepsis attenuates the expression of the iNOS gene but reduces the nitric oxide concentration.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2185-2191
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• 2012

Background: Prevalence of Barrett's esophagus (BE) in Luoyang, China, has not been reported, and its pathogenesis is controversial. The aim of this study was therefore to investigate the prevalence of BE and its underlying factors in the city of Luoyang. Method: This was a prospective study in one center. Many patients were analyzed using endoscopy who showed upper gastrointestinal symptoms between August 2006 and June 2007. In addition, the effect of apoptosis-related proteins and heat shock proteins upon BE's pathogenesis were also investigated by an immunohistochemical protocol. Results: Prevalence of BE was at 4.55% and the mean age of those affected was about 10 years older than for esophagitis. Typical reflux symptoms were significantly lower than with esophagitis, whereas signs of caspase-3 and HSP105 elevation were significantly higher. Expression of TERT, HSP70 and $HSP90{\alpha}$ in BE cases was significantly lower than in esophagitis. However, there was no statistical difference between the two groups in expression of HSP27. Conclusions: The prevalence of BE is high in Luoyang, which could result from esophagitis despite typical reflux symptoms being relatively uncommon. Initiation and development of BE might be the result of accelerated proliferation, apoptosis and differentiation of original cells to intestinal epithelium.

• 한국가금학회지
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• 제46권2호
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• pp.77-86
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• 2019

본 연구는 겨울철에 발생하여 육성된 닭들과 여름철에 발생하여 육성된 닭들 간의 열 스트레스 반응 정도와 생산능력을 비교 분석하고자 하였다. 공시계로는 겨울철에 발생된 한국토종종계 초생추 1,156수와 여름철에 발생된 초생추 934수로 총 2,090수를 분석 대상으로 하였다. 스트레스 반응정도와 생산능력을 비교하기 위하여 텔로미어의 함량과 heat shock proteins(HSPs)의 유전자 발현율을 분석하고, 생존율, 산란율 및 체중을 조사하였다. 분석 결과, HSP-70, $HSP-90{\alpha}$ 및 $HSP-90{\beta}$ 유전자 발현율은 겨울철에 발생하여 육성된 닭들이 여름철에 발생하여 육성된 닭들에 비하여 모두 유의하게 높은 발현값을 나타내었다. 텔로미어 함량은 겨울철과 여름철에 발생한 닭들 간에 유의한 차이가 없었다. 생존율에서는 여름철 발생하여 육성된 닭들이 겨울철에 발생하여 육성된 닭들에 비해 유의하게 높았고, 산란율 및 난중 또한 여름철 발생 계군이 높게 나타났다. 반면, 초산일령은 겨울철 발생 계군이 여름철 발생 계군에 비해 빨랐다. 체중에 있어서 24주까지는 겨울철 발생 계군이 여름철 발생 계군에 비해 높았으나, 28주 이후부터 발생 계군 간 역전된 결과를 보였다. 결론적으로 여름철에 발생하여 육성된 닭들이 겨울철에 발생하여 육성된 닭들에 비해 열 스트레스에 대한 저항성이 높고 생산성이 우수함을 보였다. 이는 발생 및 육성 초기에 고온에 노출된 닭들이 상대적으로 높은 열적응성을 습득한 결과로 사료된다.

• Asian-Australasian Journal of Animal Sciences
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• 제23권4호
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• pp.437-443
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• 2010

To be economically profitable, the poultry industry demands an increase in stocking density, which could adversely affect chicken welfare. The current study was performed to investigate the effect of stocking density on stress-related, heat shock protein genes (HSP70 and HSP90), 3-hydroxyl-3-methyl-glutaryl coenzyme A reductase (HMGCR) gene and telomere length in broiler chickens. Seven-day-old broiler chickens were housed at High (0.0578 $m^2$/bird), Standard (0.077 $m^2$/bird) and Low (0.116 $m^2$/bird) stocking densities with 8 replicates each until 35 d of age. The growth performance, such as body weight gain and average daily feed intake, was found to be significantly (p<0.05) higher in the Low density group, but these parameters did not show any difference between the High and Standard groups. Other growth performance, such as feed conversion ratio and final feed intake, showed no difference among the treated groups. The expression levels of HSP70 and HMGCR were found to be elevated with the increase of stocking density. The expression level of these genes was significantly (p<0.05) higher in the High density stocked group compared with the other groups, whereas the expression levels were not significantly different between the Low and Standard groups. The expression levels of HSP90 did not show any significant changes among the treated groups. The telomeric length of the birds housed in High density was reduced significantly (p<0.05) when compared to that of the birds in Low density. These results clearly indicate that birds stocked at high density show physiological adaptive changes indicative of stress at gene transcriptional and telomere levels.

• Genomics & Informatics
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• 제2권2호
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• pp.67-74
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• 2004

Cells consistently face stressful conditions, which cause them to modulate a variety of intracellular processes and adapt to these environmental changes via regulation of gene expression. Hyperosmotic and oxidative stresses are significant stressors that induce cellular damage, and finally cell death. In this study, oligonucleotide microarrays were employed to investigate mRNA level changes in cells exposed to hyperosmotic or oxidative conditions. In addition, since heat shock protein 70 (HSP70) is one of the most inducible stress proteins and plays pivotal role to protect cells against stressful condition, we performed microarray analysis in HSP70-overexpressing cells to identify the genes expressed in a HSP70-dependent manner. Under hyperosmotic or oxidative stress conditions, a variety of genes showed altered expression. Down­regulation of protein phosphatase1 beta (PP1 beta) and sphingosine-1-phosphate phosphatase 1 (SPPase1) was detected in both stress conditions. Microarray analysis of HSP70-overexpressing cells demonstrated that diverse mRNA species depend on the level of cellular HSP70. Genes encoding Iysyl oxidase, thrombospondin 1, and procollagen displayed altered expression in all tested conditions. The results of this study will be useful to construct networks of stress response genes.

• 생명과학회지
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• 제24권2호
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• pp.105-111
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• 2014

본 연구의 목적은 말의 열충격 단백질 유전자의 특성을 구명하고 말의 각 조직과 운동 전과 후 혈액에서 열충격 단백질 유전자의 발현량을 분석함에 있다. 이전의 연구를 통해, 대표적인 경주마인 더러브렛의 혈액과 골격근에서 운동 전, 후 RNA-sequencing을 통해 차등발현유전자 분석을 실시하고, 본 연구를 위해 운동 전과 후에 차등 발현된 유전자 중, 열충격 단백질 유전자(HspH1, Hsp90${\alpha}$, Hsp70)를 선택하였다. 세 개의 열충격 단백질 유전자는 각각의 혈액이나 근육에서 운동 전에 비해 후에 발현이 증가된 것으로 확인됐다. 본 연구팀은 선정된 유전자에 대한 검증과 분석을 위해, 말의 조직별 RT-PCR 분석과 운동시간별 백혈구에서 real time qPCR 분석을 실시하였다. 그 결과 말의 각 조직(갑상선, 결장, 골격근, 맹장, 신장, 심장, 척수, 폐)에서 세 개의 열충격 단백질 유전자 mRNA가 모두 존재함을 알 수 있었다. 또한, 말의 운동 시간 별 혈액에서 mRNA를 추출하여 열충격 단백질의 운동 시간에 따른 발현 양상 분석을 실시한 결과, 운동 전에 비해 운동 120분 후 열충격 단백질 유전자의 발현량이 증가함을 확인하였다. 이러한 결과는 인간과 다른 동물 실험의 결과와 일치하며, 열충격 단백질 유전자 전사 조절기작이 종간에 보존이 되어왔음을 시사한다. 또한, 운동에 따른 열충격 단백질 유전자의 발현 양상과 운동 수행 및 회복 기작간의 상관관계에 대한 추가적인 연구가 필요함을 제안하는 바이다.

• 한국환경생물학회:학술대회논문집
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• 한국환경생물학회 2002년도 학술대회
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• pp.123-126
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• 2002

Pollutants that are persistent, bioaccurnulative, and toxic have been linked to numerous adverse effects in human and animals, PBTs include heavy metals, polychlorinated biphenyls (PCBs), dioxins, polycyclic aromatic compounds (PACs) in addition to pesticides. This study focuses on toxic effects of the PBTs except pesticides on insects. Eight PBTs were selected from subgroups: three heavy metals (Pb, Hg, and Cd), two PCB mixtures (Aroclor mixtures 1 and 2), 2,3,7,8-tetrachlorodibenzo-p-dioxin, two monophenols (4-octylphenol and 4-nonylphenol), and tetrabutyltin, Beet armyworm, Spodoptera exigua, was used as test target insect species. Three physiological markers (metamorphosis, immune reaction, and follicle patency) were assessed in each exposure to different doses of the PCBs. Heat-shock proteins as molecular markers were also analyzed in response to the PCBs. All tested PBTs were toxic to metamorphosis from larvae to pupae when they were applied with diet. Two PCB mixtures were the most toxic compounds in this assay by giving significant toxicity at 0.005 ppm, while others had from 10 to 1000 ppm. Dioxin (0.1 ppb), tetrabutyltin (0.1 ppb), Pb (10 ppb), and Hg (0,01 ppb) were potent to inhibit immune reactions analyzed by inducing phenoloxidase activity and blocked phospholipase $A_2$ enzyme, Tetrabutyltin and dioxin significantly induced follicle cell patency, but their effects were lower than that of endogenous juvenile hormone, Dioxin, Pb, Hg, and Cd could induce the expression of heat shock proteins that were detected by immunoblotting against human HSP70 monoclonal antibody. HSP78 and HSP80 were upregulated in response to the PBTs. This expression was detected from the fat body and epidermis at as fast as 4h after injection. All these results clearly suggest that PBTs give significant ecotoxicity to insects that are valuable organisms in our environment.