• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.457-465
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• 2018

The expression of BCL-2 interacting cell death suppressor (BIS), an anti-stress or anti-apoptotic protein, has been shown to be regulated at the transcriptional level by heat shock factor 1 (HSF1) upon various stresses. Recently, HSF1 was also shown to bind to BIS, but the significance of these protein-protein interactions on HSF1 activity has not been fully defined. In the present study, we observed that complete depletion of BIS using a CRISPR/Cas9 system in A549 non-small cell lung cancer did not affect the induction of heat shock protein (HSP) 70 and HSP27 mRNAs under various stress conditions such as heat shock, proteotoxic stress, and oxidative stress. The lack of a functional association of BIS with HSF1 activity was also demonstrated by transient downregulation of BIS by siRNA in A549 and U87 glioblastoma cells. Endogenous BIS mRNA levels were significantly suppressed in BIS knockout (KO) A549 cells compared to BIS wild type (WT) A549 cells at the constitutive and inducible levels. The promoter activities of BIS and HSP70 as well as the degradation rate of BIS mRNA were not influenced by depletion of BIS. In addition, the expression levels of the mutant BIS construct, in which 14 bp were deleted as in BIS-KO A549 cells, were not different from those of the WT BIS construct, indicating that mRNA stability was not the mechanism for autoregulation of BIS. Our results suggested that BIS was not required for HSF1 activity, but was required for its own expression, which involved an HSF1-independent pathway.

• The Journal of Korean Medicine
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• v.27 no.2 s.66
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• pp.70-85
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• 2006

Objectives; This study examined the neuroprotective effect of Hyulbuchookautang (血府逐瘀湯, HBCAT)against neural damage following focal cerebral infarction. Methods : Sprague-Dawley Rats were induced with focal cerebral infarction by temporal middle cerebral artery occlusion (MCAO). The rats were divided into 2 groups. We treated extract of HBCAT to one group after operation (sample group), and the other group wasn't treated after operation (control group). We observed neurological scores and TIC-stained infarct area, total infarct volume in brain sections and Bax-positive neurons, HSP70- positive neurons in brain regions. Results : HBCAT treatment at 3 days after MCAO reduced neurological scores induced by MCAO. HBCAT treatment at 5 days after MCAO reduced TTC-stained infarct area in brain sections induced by MCAO. HBCAT treatment at 5 days after MCAO reduced total infarct volume in brain sections induced by MCAO. HBCAT treatment after MCAO reduced Bax-positive neurons in cortex infarct core and cortex infarct penumbra and caudo-putamen of brain regions induced by MCAO. HBCAT treatment after MCAO reduced HSP70- positive neurons in cortex infarct penumbra of brain regions induced by MCAO. Conclusions : These results suggest that HBCAT has a neuroprotective effect against focal cerebral ischemia.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5243-5248
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• 2013

Background: Triptolide, extracted from the herb Tripteryglum wilfordii Hook.f that has long been used as a natural medicine in China, has attracted much interest for its anti-cancer effects against some kinds of tumours in recent years. Artesunate, extracted from the Chinese herb Artemisia annua, has proven to be effective and safe as an anti-malarial drug that possesses anticancer potential. The present study attempted to clarify if triptolide enhances artesunate-induced cytotoxicity in pancreatic cancer cell lines in vitro and in vivo. Methods: In vitro, to test synergic actions, cell viability and apoptosis were analyzed after treatment of pancreatic cancer cell lines with the two agents singly or in combination. The molecular mechanisms of apoptotic effects were also explored using qRT-PCR and Western blotting. In vivo, a tumor xenograft model was established in nude mice, for assessment of inhibitory effects of triptolide and artesunate. Results: We could show that the combination of triptolide and artesunate could inhibit pancreatic cancer cell line growth, and induce apoptosis, accompanied by expression of HSP 20 and HSP 27, indicating important roles in the synergic effects. Moreover, tumor growth was decreased with triptolide and artesunate synergy. Conclusion: Our result indicated that triptolide and artesunate in combination at low concentrations can exert synergistic anti-tumor effects in pancreatic cancer cells with potential clinical applications.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.4
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• pp.205-212
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• 2010

Endometritis is one of the primary reasons for reproductive failure. In order to investigate endometritis-associated marker proteins, proteomic analysis was performed on bovine endometrium with endometritis. In bovine endometritis, desmin, $\alpha$-actin-2, heat-shock protein (HSP) 27, peroxiredoxin-6, luteinizing hormone receptor isoform 1, collectin-43 precursor, deoxyribonuclease-I (DNase-I), and MHC class I heavy chain (MHC-Ih) were up-regulated. In contrast, transferrin, interleukin-2 precursor, hemoglobin $\beta$ subunit, and potassium channel tetramerisation domaincontaining 11 (KCTD11) were down-regulated in comparison to normal endometrium. The proteomic results were validated by semiquantitative-PCR and immunoblot analysis. The mRNA levels of desmin, transferrin, $\alpha$-actin-2, HSP27, KCTD11, and MHC-Ih were up-regulated by over 1.5-fold, and showed a pattern similar to their proteomic profiles. Desmin and $\alpha$-actin-2 protein showed positive correlations between proteomic analysis and immunoblot analysis. These results suggest that desmin and $\alpha$-actin-2 may play important roles in endometritis-related function, and could be useful markers for the diagnosis of bovine endometritis.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.2
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• pp.107-113
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• 2009

Olibanum (Boswellia serrata) has been shown to have anti-inflammatory, anti-arthritic and anticancer effects. This study determined the role of a water extract of olibanum in platelet-derived growth factor (PDGF)-stimulated proliferation and migration of rat aortic smooth muscle cells (RASMCs). PDGF-BB induced the migration and proliferation of RASMCs that were inhibited by olibanum extract in a dose-dependent manner. The PDGF-BB-increased phosphorylation of p38 mitogen-activated protein kinase (MAPK); the heat shock protein (Hsp) 27 was significantly inhibited by the olibanum extract. The effects of PDGF-BB-induced extracellular signal-regulated kinase1/2 was not altered by the olibanum extract. Treatment with olibanum extract inhibited PDGF-BB-stimulated sprout out growth of aortic rings. These results suggest that the water extract of olibanum inhibits PDGF-BB-stimulated migration and proliferation in RASMCs as well as sprout out growth, which may be mediated by the inhibition of the p38 MAPK and Hsp27 pathways.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.20 no.1
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• pp.29-40
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• 2010

This study was aimed at investigating the gene expression profile in basal ganglia of cadmium exposed rat based on cDNA array analysis. For cDNA array analysis, adult Sprague-Dawley male rats (350 ${\pm}$ 25 g) were intraperitoneally injected with 2.0 mg/kg body weight/day of CdCl2 (0.3 ml) for 5 days. For doserelated gene expression analysis rats were intraperitoneally injected with 0.0, 0.1, 0.3, 1.0 mg/kg body weight/day of CdCl$_2$ for 5 days. Control rats were injected with equal volume of saline. Cadmium concentration of brain was analyzed by atomic absorption spectrophotometer. For cDNA array, RNA samples were extracted from basal ganglia and reverse-transcribed in the presence of [${\alpha}$32P]-dATP. Membrane sets of the Atlas Rat 1.2 array II and Toxicology array 1.2 (Clontech, Palo Alto, CA) were hybridized with cDNA probe sets. RT-PCR was employed to validate the relative gene expression patterns obtained from the cDNA array. Northern blot hybridization methods were employed to assess the dose-related gene expression. Among the 2352 cDNAs, 671 genes were detected in both array sets and 63 genes of 38 classes showed significant (more than two fold) changes in expression. Thirty five of these genes were up-regulated and twenty eight were down-regulated in the cadmium exposed group. According to the dose-related gene expression analysis, heat shock 27 kDa protein (HSP27), neurodegeneration-associated protein 1 (Neurodap 1) genes were significantly up-regulated and melatonin receptor 1a (Mel1a), Kinesin family member 3C (KIF3C), novel kinesinrelated protein (KIF1D) genes were significantly downregulated even in the low-dose of cadmium exposed group (0.1 mg/kg body weight/day). Conclusions Sixty three genes detected in this study can give some more useful informations about the cadmium-induced neurotoxicity in the basal ganglia. As well as, HSP27, Neurodap1, Mel1a, KIF3C and KIF1D genes may be useful for the study of the cadmium-induced neurotoxicity because these genes showed dramatic changes of mRNA levels in response to the low dose of cadmium exposure.

• Journal of Society of Preventive Korean Medicine
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• v.13 no.1
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• pp.13-27
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• 2009

This study aimed to validate neuroprotective effect of Chungpaesagan-tang on the early stage of cerebral ischemic damage. Cerebral ischemic damage was induced by the middle cerebral artery occlusion (MCAO) for 2 hours in the Sprague-Dawley rats. Water extract of Chungpaesagan-tang(8.7g/kg) was administered orally twice at 1 and 4 hours after the MCAO. Neurological score was tested at 3 and 24 hours after the MCAO and Chungpaesagan-tang administration. At 24 hours after the MCAO, infarct volume and edema ratio was evaluated with the TTC staining. Apoptotic cell death in cerebral cortex and caudate putamen was observed with cresyl violet staining and TUNEL labeling. Bax expression in the MCAO rat brain was stained with immunohistochemistry. Chungpaesagan-tang improved neurological and behavioral impairment of the MCAO rats and reduced infarct area, infarct volume and brain edema formation. Chungpaesagan-tang attenuated cell death percentage in cortex penumbra and reduced TUNEL positive cells in cortex penumbra and in caudate putamen of the MCAO rats. Chungpaesagan-tang reduced Bax positive neurons in caudate putamen and reduced c-Fos positive neurons in cortex penumbra of the MCAO rats. Chungpaesagan-tang intensified neuronal HSP72 expression in cortex penumbra of the MCAO rats. In results, Chunpaesagan-tang reduces infarct volume and edema formation through anti-apoptotic effect. This result suggests that Chunapaesagan-tang has an adequate neuroprotective effect on the early stage of cerebral ischemic damage.

• Journal of Pharmaceutical Investigation
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• v.39 no.4
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• pp.257-261
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• 2009

Effective therapeutics for renal failures have not yet been developed until now. Recently, there was a report showing that Wen-pi-tang-Hab-Wu-ling-san (WHW) prescriptions had the potential to prevent renal failures through the increased expression of HSP-27 and HSP-72 after ischemia/reperfusion. Therefore, formulation studies by pH-specific released systems were carried out to exhibit the optimal activity of WHW prescriptions in this study. WHW prescriptions were separately extracted using water into two parts of stomach-released (SR) and intestine-released (IR) extracts. Subsequently, the double-layered tablet was prepared using the SR extracts and pharmaceutical additives and enteric-coated IR tablet. Dissolution studies were carried out to figure out the release of cinnamic acid and icarrin from SR tablet, IR tablet and double-layered tablet, respectively. The complete release of cinnamic acid from SR tablet showed 90min after dissolution in pH 1.2 and insignificant drug released from IR tablet. As well as, icarrin from IR tablet completely released in pH 6.8 and 7.4 as enteric-coating film dissolved.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.2
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• pp.246-253
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• 2017

Objective: Present study explores the effect of hot summer period on the glycolytic rate of early post-mortem meat quality of Ghungroo and Large White Yorkshire (LWY) pig and comparative adaptability to high temperature between above breeds by shifting the expression of stress related genes like mono-carboxylate transporters (MCTs) and heat shock proteins (HSPs). Methods: Healthy pigs of two different breeds, viz., LYW and Ghungroo (20 from each) were maintained during hot summer period (May to June) with a mean temperature of about $38^{\circ}C$. The pigs were slaughtered and meat samples from the longissimus dorsi (LD) muscles were analyzed for pH, glycogen and lactate content and mRNA expression. Following 24 h of chilling, LD muscle was also taken from the carcasses to evaluate protein solubility and different meat quality measurements. Results: LWY exhibited significantly (p<0.01) higher plasma cortisol and lactate dehydrogenase concentration than Ghungroo indicating their higher sensitivity to high temperature. LD muscle from LWY pigs revealed lower initial and ultimate pH values and higher drip loss compared to Ghungroo, indicating a faster rate of pH fall. LD muscle of Ghungroo had significantly lower lactate content at 45 min postmortem indicating normal postmortem glycolysis and much slower glycolytic rate at early postmortem. LD muscle of LWY showed rapid postmortem glycolysis, higher drip loss and higher degrees of protein denaturation. Ghungroo exhibited slightly better water holding capacity, lower cooking loss and higher protein solubility. All HSPs (HSP27, HSP70, and HSP90) and MCTs (MCT1, MCT2, and MCT4) in the LD muscle of pigs inclined to increase more in Ghungroo than LWY when exposed to high temperature. Conclusion: Effect of high temperature on the variation of HSPs and MCTs may play a crucial role in thermal tolerance and adaptation to different climatic conditions, pH regulation, muscle acidification, drip loss, protein denaturation and also in postmortem meat quality development.

• Childhood Kidney Diseases
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• v.11 no.1
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• pp.106-111
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• 2007

[ $Henoch-Sch\ddot{o}nlein$ ] Purpura(HSP) is a form of vasculitis that typically affects small arteries in the skin, joints, intestinal tract and kidneys. It usually resolves spontaneously but sometimes can cause serious problems in the kidneys and intestinal tract. A 6-year-old girl with purpura, arthralgia and abdominal pain for 2 weeks was admitted. She also showed gross hematuria, generalized edema and decreased urine output. Blood pressure was in the upper normal range. Initial laboratory findings showed hypoalbuminemia, hyperlipidemia, microhematuria and nephrotic-range proteinuria(27.2 g/day). Initially, she was treated with pulse methylprednisolone, azathioprine, albumin and furosemide. Her renal biopsy revealed diffuse mesangial proliferation with strong IgA deposition. There were no crescents. On the third hospital day, she complained of severe abdominal pain and free peritoneal air was seen on abdominal X-ray. Primary repair of small bowel was performed and two pin-point sized holes were found. One week later, she still showed heavy proteinuria. Therefore, we added an ACE inhibitor and dipyridamole, and changed azathioprine to cyclosporine. One month later, the urine protein/creatinine ratio was decreased to 17.8 from 57, but heavy proteinuria has been still persisted. Here we report a rare case of a patient with HSP who had both severe nephrritc-nephrotic syndrome and small bowel perforation.