• Molecules and Cells
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• v.27 no.5
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• pp.533-538
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• 2009

Heat shock protein 27 (Hsp27) is a molecular chaperone protein which regulates cell apoptosis by interacting directly with the caspase activation components in the apoptotic pathways. With the assistance of the Tat protein transduction domain we directly delivered the Hsp27 into the myocardial cell line, H9c2 and demonstrate that this protein can reverse hypoxia-induced apoptosis of cells. In order to characterize the contribution of Hsp27 in blocking the two major apoptotic pathways operational within cells, we exposed H9c2 cells to staurosporine and cobalt chloride, agents that induce mitochondria-dependent (intrinsic) and -independent (extrinsic) pathways of apoptosis in cells respectively. The Tat-Hsp27 fusion protein showed a greater propensity to inhibit the effect induced by the cobalt chloride treatment. These data suggest that the Hsp27 predominantly exerts its protective effect by interfering with the components of the extrinsic pathway of apoptosis.

• BMB Reports
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• v.46 no.1
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• pp.47-52
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• 2013

Intestinal epithelial cell (IEC) apoptosis induced by hypoxia compromise intestinal epithelium barrier function. Both Akt and Hsp90 have cytoprotective function. However, the specific role of Akt and $Hsp90{\beta}$ in IEC apoptosis induced by hypoxia has not been explored. We confirmed that hypoxia-induced apoptosis was reduced by $Hsp90{\beta}$ overexpression but enhanced by decreasing $Hsp90{\beta}$ expression. $Hsp90{\beta}$ overexpression enhanced BAD phosphorylation and thus reduced mitochondrial release of cytochrome C. Reducing $Hsp90{\beta}$ expression had opposite effects. The protective effect of $Hsp90{\beta}$ against apoptosis was negated by LY294002, an Akt inhibitor. Further study showed that Akt phosphorylation was enhanced by $Hsp90{\beta}$, which was not due to the activation of upstream PI3K and PDK1 but because of stabilization of pAkt via direct interaction between $Hsp90{\beta}$ and pAkt. These results demonstrate that $Hsp90{\beta}$ may play a significant role in protecting IECs from hypoxia-induced apoptosis via stabilizing pAkt to phosphorylate BAD and reduce cytochrome C release.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.4
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• pp.319-324
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• 2000

The causal relationship between heat shock protein (HSP) and second window of cardioprotective effect is still undetermined. In the present study, we assessed whether HSP-producing substances, amphetamine and ketamine, afforded protection against reperfusion-induced ventricular fibrillation (VF) and these protective effect remained after the inhibition of HSP72 production by quercetin, a mitochondrial ATPase inhibitor. Adult mongreal male cats $(n=60,\;2.5{\sim}4\;kg)$ were used in this study. Experimental animals were divided into five groups; control group (n=15), amphetamine ('A', n=11) group, ketamine ('K', n=9) group, amphetamine-ketamine ('AK', n=16) group and amphetamine-ketamine-quercetin ('AKQ', n=9) group. Twenty-four hours after the drug treatment, an episode of 20-min coronary artery occlusion was followed by 10-min reperfusion. The incidence of reperfusion-induced VF in the AK and AKQ groups was significantly lower than that in control group (p＜0.01). After the ischemia/reperfusion procedure, western blot analysis of HSP72 expression in the myocardial tissues resected from each group was performed. HSP72 production in the AK group was marked, whereas HSP72 was not detected in the AKQ and control groups. These results suggest that the suppressive effect against reperfusion-induced VF induced by amphetamine and ketamine is not mediated by myocardial HSP72 production but by other mechanisms.

• Korean Journal of Exercise Nutrition
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• v.13 no.2
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• pp.161-167
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• 2009

The purpose of this study was to investigate whether two different exercises, acute exhaustive exercise and long-term endurance exercise training could affect to the expression of Mn-SOD, HSP70, and PPAR-γ protein in myocardium. The Wistar-Kyoto rats(n=24, 4 weeks) were used and randomly divided into 3 groups; endurance exercise training group (EET, n=8), acute exhaustive exercise group (AEE, n=8) or control group (CON, n=8). EET performed treadmill exercise for 12 weeks (5 days/week, 30~60 min/day). AEE exercised treadmill running (speed increased gradually to 14-26 m/min, 60 min ±10min) until exhausted when EET finished the program. Then, all the rats were sacrificed 48 hours rest at least after the last session of their own exercise program. Hearts were isolated and then the expression of Mn-SOD, HSP70, and PPAR-γ were analyzed by western blotting. One-way repeated ANOVA was used and p value under 0.05 was considered as statistical significance. The results were followed as; the expression of Mn-SOD of AEE was decreased compared with CON. However, the expression of Mn-SOD of EET was increased compared with CON. There was significant difference between AEE and EET in the expression of Mn-SOD. The expressions of HSP70 and PPAR-γ in the both AEE and EET were significantly increased compared with CON. In conclusion, acute exhaustive exercise might induce oxidative stress wheres endurance exercise training could ameliorate the oxidative conditions by increase of Mn-SOD, HSP70, and PPAR-γ. Therefore, we suggested that endurance exercise training could enhance the complementary antioxidant system and improve to prevent apoptosis. Further, a long-term moderat aerobic exercise program might play a important role in mitochondrial biogenesis in the heart.

• Molecules and Cells
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• v.27 no.6
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• pp.703-703
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• 2009

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4267-4271
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• 2013

Background: As natural medicines in Asia, curcumin and triptolide extracted from different drug plants have proven to possess anticancer potential and widely used for anti-cancer research. The present study attempted to clarify that curcumin and triptolide synergistically suppress ovarian cancer cell growth in vitro. Methods: To test synergic effects, cell viability and apoptosis were analyzed after curcumin and triptolide combination treatment on ovarian cancer cell lines. Synergistic effects on apoptosis induction were determined by lactate dehydrogenase (LDH) leakage assay, intracellular reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) loss assay and flow cytometry analysis. Critical regulators of cell proliferation and apoptosis related were analyzed by qRT-PCR and Western blotting. Results: We showed that the combination of curcumin and triptolide could synergistically inhibit ovarian cancer cell growth, and induce apoptosis, which is accompanied by HSP27 and HSP70, indicating that HSP27 and HSP70 play the important role in the synergic effect. Conclusions: From the result present here, curcumin and triptolide combination with lower concentration have a synergistic anti-tumor effect on ovarian cancer and which will have a good potential in clinical applications.

• Interdisciplinary Bio Central
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• v.5 no.4
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• pp.9.1-9.7
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• 2013

Introduction: Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial heat shock protein (HSP), which belongs to HSP90 family. It plays important roles in regulating mitochondrial integrity, protecting against oxidative stress, and inhibiting cell death. Recent studies suggest that TRAP1 is linked to mitochondria and its metabolism. In this study, we established TRAP1 transgenic mice and performed partial hepatectomy (PH) on wild-type (WT) and TRAP1 transgenic mice to investigate the function of TRAP1 during liver regeneration. Results and Discussion: We found that TRAP1 was highly expressed in liver as well as kidney. In addition, liver regeneration slightly decreased together with increased fatty liver and inflammation at 72 hr after PH in TRAP1 transgenic mice compared with WT control group mice. Concomitantly, we observed decreased levels of p38 protein in TRAP1 transgenic mice compared with WT control group mice. These results suggest that TRAP1 plays a critical role in liver energy balance by regulating lipid accumulation during liver regeneration. Conclusions and Prospects: To our knowledge, we reported, for the first time, that liver regeneration slightly reduced together with increased fat accumulations after PH in TRAP1 transgenic mice compared with WT control group mice. Concomitantly, we observed decreased levels of p38 protein in TRAP1 transgenic mice compared with WT control group mice. Overexpression of TRAP1 might affect liver regeneration via disturbing mitochondrial function leading to fatty liver in vivo.

• Journal of The Korean Society of Grassland and Forage Science
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• v.38 no.3
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• pp.170-174
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• 2018

Environmental stresses caused by climate change, such as high temperature, drought and salinity severely impact plant growth and productivity. Among these factors, high temperature stress will become more severe during summer. In this study, we examined physiological and molecular responses of maize plants to high temperature stress during summer. Highest level of $H_2O_2$ was observed in maize leaves collected July 26 compared with June 25 and July 12. Results indicated that high temperature stress triggers production of reactive oxygen species (ROS) in maize leaves. In addition, photosynthetic efficiency (Fv/Fm) sharply decreased in leaves with increasing air temperatures during the day in the field. RT-PCR analysis of maize plants exposed to high temperatures of during the day in field revealed increased accumulation of mitochondrial and chloroplastic small heat shock protein (HSP) transcripts. Results demonstrate that Fv/Fm values and organelle-localized small HSP gene could be used as physiological and molecular indicators of plants impacted by environmental stresses.

• Molecules and Cells
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• v.46 no.6
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• pp.374-386
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• 2023

Thermal stress induces dynamic changes in nuclear proteins and relevant physiology as a part of the heat shock response (HSR). However, how the nuclear HSR is fine-tuned for cellular homeostasis remains elusive. Here, we show that mitochondrial activity plays an important role in nuclear proteostasis and genome stability through two distinct HSR pathways. Mitochondrial ribosomal protein (MRP) depletion enhanced the nucleolar granule formation of HSP70 and ubiquitin during HSR while facilitating the recovery of damaged nuclear proteins and impaired nucleocytoplasmic transport. Treatment of the mitochondrial proton gradient uncoupler masked MRP-depletion effects, implicating oxidative phosphorylation in these nuclear HSRs. On the other hand, MRP depletion and a reactive oxygen species (ROS) scavenger non-additively decreased mitochondrial ROS generation during HSR, thereby protecting the nuclear genome from DNA damage. These results suggest that suboptimal mitochondrial activity sustains nuclear homeostasis under cellular stress, providing plausible evidence for optimal endosymbiotic evolution via mitochondria-to-nuclear communication.

• Journal of Microbiology and Biotechnology
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• v.28 no.4
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• pp.542-550
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• 2018

Heat shock protein 90 (Hsp90) is treated as a molecular therapeutic target for the prevention and treatment of cancer. Geldanamycin (GA) was the first identified natural Hsp90 inhibitor, but hepatotoxicity has limited its clinical application. Nevertheless, a new GA analog (WK-88-1) with the non-benzoquinone skeleton, obtained from genetically engineered Streptomyces hygroscopicus, was found to have anticancer activity against two human breast cancer cell lines. WK-88-1 produced concentration-dependent inhibition of cell proliferation, cell cycle arrest, and apoptosis in estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 cell lines. Detailed analysis showed that WK-88-1 downregulated some key cell cycle molecules (CDK1 and cyclin B1) and lead to $G_2/M$ cell cycle arrest. Further studies also showed that WK-88-1 could induce human breast cancer cell apoptosis by downregulating Hsp90 client proteins (Akt, p-Akt, IKK, c-Raf, and Bcl-2), decreasing the ATP level, increasing reactive oxygen species production, and lowering the mitochondrial membrane potential. Meanwhile, we discovered that WK-88-1 significantly decreased the levels of Her-2 and $ER-{\alpha}$ in MCF-7 cells but not in MDA-MB-231 cells. In addition, WK-88-1 significantly increased caspase-3, -8, and -9 activities and the cleavage of PARP in a concentration-dependent manner (with the exception of caspase-3 and PARP in MCF-7 cells). Taken together, our preliminary results suggest that WK-88-1 has the potential to play a role in breast cancer therapy.