• Biomolecules & Therapeutics
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• v.17 no.1
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• pp.25-31
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• 2009

Clusterin is a heterodimeric sulfated glycoprotein and plays a role in many different types of cancer as a cell survival factor and helps cancerous cells to evade stress-induced apoptosis. To investigate whether the regulation of clusterin expression is involved in the mechanism of anticancer agent, we studied the effect of tamoxifen on clusterin expression in human prostate cancer PC-3 cells. Treatment of PC-3 cells with tamoxifen reduced cellular proliferation. Western blot analyses showed that treatment with tamoxifen suppressed clusterin expression in a concentration-dependent manner. Transfection with clusterin siRNA plasmid showed that clusterin is required for PC-3 cell survival. We found that tamoxifen resulted in a rapid decrease in the phosphorylation of Akt on Ser473 leading to prevent kinase activity. Expression of myristoylated Akt prevented tamoxifen-mediated clusterin downregulation. Interestingly, MG132, a wellknown proteasome inhibitor also recovered clusterin expression suppressed by tamoxifen. These data indicate that clusterin expression may be regulated by activation of Akt and ubiquitin-proteasome pathway plays an important role in tamoxifen-mediated clusterin suppression.

• Journal of Life Science
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• v.20 no.4
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• pp.584-588
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• 2010

Clusterin is an 80 kDa heterodimetric glycosylated protein which plays diverse biological roles in various tissues and organs. Clusterin is reported to be associated with the pathogenesis of coronary artery disease and atherosclerosis. Therefore, we investigated the genotype for the T

• Journal of Microbiology and Biotechnology
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• v.14 no.6
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• pp.1333-1337
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• 2004

Oxidants such as hydrogen peroxide are powerful inducers of cell damage, ageing, and apoptosis. Since clusterin, a 75-80 kDa mammalian glycoprotein, is frequently found to be inducible in apoptotic cells and tissues, this study inquired into whether this would be a protective mechanism against further cell death. The aim was to find out whether overexpression of clusterin could protect cells from oxidant­induced stress and apoptosis. To clarify this issue, we generated and analyzed stable cell lines expressing fusion proteins of a rat clusterin with an enhanced green fluorescent protein (EGFP). When treated with varying concentrations of hydrogen peroxides, clusterin transfectants indeed showed increased resistance to apoptosis and exhibited a much higher survival rate than mock-transfected cells. On the other hand, neither intracellular re-distribution nor local concentration of clusterin-EGFP was observed, which leaves the question open about its anti-apoptotic mechanism. In conclusion, the overexpression of clusterin provides a means for protecting cells against oxidative stress and subsequent cell death.

• Journal of Oral Medicine and Pain
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• v.22 no.2
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• pp.341-358
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• 1997

Clusterin is a highly glycosylated protein composed of two disulfide linked subunits. Although its biolobical action is not clearly defined, clusterin seems to be involved not only in remodeling of damaged tissue, but also in production of halitosis, the present study was designated to elucidate the expression of clusterin in the salivary gland of diabetic rats. For this study, 24 Sprague-Dawley rats were used for the experiment and divided into 2groups: control and experimental. The experimental group was composed of 18 rats and the control goup was 6 rats. After nduction of diabetes by STZ injection, the animals were sacrificed at 1,3,5,7,10,14 days. The parotid and submamndibular glands were observed histologically and the transcriptional expression of clusterin in the glands by Northern blot. The finding were as follows : 1. In experimental group, the salivary glands were observed at day 3 and then a seven destructive pattern was found in the glands at day 5. Howere, regeneration of gland tissue occured at day 14. 2. In experimental goup, destructive change was examined in the septal connective tissue after 7 days, and gradually more serious. 3. In experimental group, clusterin was expressed in the submandibular glands after 5 days, but in parotid glands to a lesser extent after 10 days. These results suggest that clusterin seems to be closely associated with histologic changes in the mucous glands rather serous glands.

• Journal of Oral Medicine and Pain
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• v.22 no.2
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• pp.395-408
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• 1997

Generally, the major causative factor of halitosis is thought to be a sulfated compounds. Clusterin, a sulfated glycoprotein-2(SGP-2), composed of two disulfide linked subunits. It is conceivable that clusterin might be one of candidated causing halitosis. We assume that clusterin found in the salivary glands under stress conditions might examine clusterin in the salivary glands under stress conditions. For this study, 24 rats were divided into 2 group : 1)18 rats of group I were bathed in cold water for 30 seconds twice a day 2) 6 rats of group II were selected as a control. The animals were sacrified at day 0,3,5,7,10, and 14 of the experiment and the submandibular glands and parotid glands were removed. RNAs were purified from the salivary glands and the transcription of clusterin in the glands was measured by Northern blot analysis. The specimens of the salivary glands were subjected to Hematoxillin-Eosin and PAS stainings and examined under the light microscope. The findings were as follows : 1. In group I, clusterin was expressed remarkably in the submandibular glands at day 5 but in the parotid glands remarkably at day 3 day slightly at day 7. 2. No significant histologic change was found in the salivary glands except that acini were slightly apart from each other under the cold stress condition.

• BMB Reports
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• v.57 no.3
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• pp.149-154
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• 2024

The stomach has emerged as a crucial endocrine organ in the regulation of feeding since the discovery of ghrelin. Gut-derived hormones, such as ghrelin and cholecystokinin, can act through the vagus nerve. We previously reported the satiety effect of hypothalamic clusterin, but the impact of peripheral clusterin remains unknown. In this study, we administered clusterin intraperitoneally to mice and observed its ability to suppress fasting-driven food intake. Interestingly, we found its synergism with cholecystokinin and antagonism with ghrelin. These effects were accompanied by increased c-fos immunoreactivity in nucleus tractus solitarius, area postrema, and hypothalamic paraventricular nucleus. Notably, truncal vagotomy abolished this response. The stomach expressed clusterin at high levels among the organs, and gastric clusterin was detected in specific enteroendocrine cells and the submucosal plexus. Gastric clusterin expression decreased after fasting but recovered after 2 hours of refeeding. Furthermore, we confirmed that stomachspecific overexpression of clusterin reduced food intake after overnight fasting. These results suggest that gastric clusterin may function as a gut-derived peptide involved in the regulation of feeding through the gut-brain axis.

• Journal of Oral Medicine and Pain
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• v.23 no.4
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• pp.309-326
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• 1998

In general, the major causative factor of halitosis is thought to be a sulfated compounds. Clusterin, a sulfated glycoprotein-2(SGP-2), is frequently found in diabetic conditions and cold stress conditions. The same result is werum glucose level to diabeteic and cold stress conditions that founded Clusterin. Therefore, this study was performed to examine Clusterin in the slivary glands under stress conditions before insulin injection I.M. Fourty rats were diveded into 3 groups ; 1) 10 rats of gorup I were selected as a control 2) 15 rats beloning to group II were bathed in cold water for 30 seconds twice a day 3) 15 rats in group III received cold stress and injected I.M. with insulin. The rats were sacrifeced at day 0, 3, 5, 7 and 10 of the experiment and the submandibular glands and parotid galnds were removed. RNAs were purified from the salivary of the salivary glands were subjected to Hematoxillin-Eosin stainings and examined under the light microscope. The obtained results were as follows : 1. With immunohistochemistric method, in normal control goup, Clusterin was moderately stained in the intercalated ductal cell of the submandibualr glands, mild stained in the striated ductal cell of the submandibular glands, heavily stained on the cytoplasm of the intercalated ductal cell in the mucous submandibular glands nad slightrly stained in the intercalated ductal cell of the paroted gland, expressed negativity in the acina cell. 2. With immunohistochemistric method, Clusterin slightly increased in the acina cell of the submandibular glands under stress condition at 3 days after experement, moderately stained at 5 days after experiment so revealed positive response. And hearily in the intercalated ductal cell and mildly lin the acina celluar eytoplasm of the parotid glands under stress condition at 3 days experiment. 3. With immunohistochemistric method, no remarkable differences are found between the normal control group and stress conditioned group that insulin administration was performed before. 4. In the stressor-giving group, Clusterin mRNA was porminently expressed in submandibular gland after 5 days after experiment, in parotid gland after 3 days after experiment, performed in immunoelectrophoresis method. 5. In the insulin-injected nad stressor-giving group, Clusterin mRNA was not observed in all experimental submandibular and parotid gland, performed in immunoelectrophoresis method.

• Biomedical Science Letters
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• v.14 no.1
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• pp.55-58
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• 2008

Clusterin is an 80 kDa heterodimetric glycosylated protein and it plays diverse biological roles in various tissues and organs. Clusterin is reported to be associated with the pathogenesis of coronary artery disease and atherosclerosis. Therefore, we investigated the genotype for the A/G polymorphism at the position 4,183 of clusterin gene in Koreans and compared genotype of patients with control group. 100 patients (Male 63, Female 37), who previously underwent coronary artery stent due to ischemic heart disease and 100 controls (Male 36, Female 64) participated in this study. There was a significant association between 4,183 A/G polymorphism in clusterin gene and coronary artery disease (CAD). The present study shows that clusterin gene A/G polymorphism may be associated with the pathogenesis of CAD. Further studies with larger population may be needed for the development of diagnostic methods at genetic level such as DNA chip.

• Journal of Oral Medicine and Pain
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• v.31 no.1
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• pp.79-89
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• 2006

The aim of this study is to know how the rat submandibular gland changes under various emotional stress condition, using molecular biological methods. Restraint and chronic unpredictable mild stress (CUMS) experiment is conducted on fifty one 7-week old Sprague-Dawley rats (restraint stress experiment: 21, CUMS: 30). The rats were sacrificed, the submandibular glands were excised immediately at certain time, and examined by the use of immunohistochemistry and western blotting. In CUMS experiment, sucrose preference test, water intake change, weight change were implemented at 1 week interval for the experimental period The results are as follows: 1. The number of clusterin-secreting cells of restraint stress group compared to control group showed significantly decreasing tendency in all experimental groups except for the 1st hour group (p<0.001 in the 9th, 24th, 72nd, 120th, and 168th hour group). 2. The number of clusterin-secreting cells of CUMS group compared to control group showed significantly increasing tendency in the 2nd week group (p<0.01), and significantly decreasing tendency in the 4th and 5th week group (p<0.001). 3. Sucrose preference test in CUMS experiment showed significant difference between the 5th week experimental group and control group (p<0.01). 4. Weight change in CUMS experiment showed significant difference between the 5th week experimental group and control group (p<0.01), but water intake change didn't show significant difference compared to control group. 5. In western blot analysis, clusterin expression was decreased on a gradual basis in due time compared to the control group in the restraint stress group. As for CUMS group (chronic unpredictable mild stress group), it was increased till the 2nd week and decreased till the 5th week after that, which is similar to immunohistochemical analysis result and the decreasing tendency of sucrose preference and weigh changes. Through the test, it was proved that expression of clusterin in saliva glands decreases after receiving either acute or chronic stress, indicating relation with depression caused by chronic stress. Unlike other data, however, apoptotic tendency was hardly found in tissues. Diverse possibilities could be suggested on that: first, the stress was not enough to expedite apoptosis; second, apoptosis-related protein was already being secreted though not detected with microscope; third, clusterin, a major secretion molecule of saliva, decreased with saliva's malfunction due to stress. In the respect, it will be necessary to examine proteins expressed in case of cell death or other heat-shock proteins at the same time, in order to see whether any cellular change or death is caused by decreasing clusterin under high stress, and whether the original state is restored as time goes by under mild stress, through longer-term tests using even higher acute stress.

• Journal of Oral Medicine and Pain
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• v.37 no.2
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• pp.81-91
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• 2012

It has been known that saliva may affect the most of oral diseases. On the contrary, several systemic conditions may affect salivary flow and cause oral dryness and psychosocial stress especially may a crucial role in the etiology of hyposalivation and oral dryness. Many studies have focused on macroscopic effects of the stress on the salivary glands by autonomic respose, but on the other hand it has hardly been reported on cellular microscopic effects of the stress on the salivary glands. Therefore, this study was performed to examine clusterin, a antiapoptotic and cytoprotective protein, in the parotid glands under restraint stress condition. For this study, 10 rats were divided into 3 groups; 1) 2 rats of group I were selected as a normal control. 2) 2 rats of group II, as a experimental control were placed in the restraint cone for 2 hours 3) 6 rats of group III were placed in the restraint cone for 2 hours once a day. The rats were sacrificed immediately(group II, as a experimental control), 24, 48, and 72 hours after application of the stress and the parotid glands were excised. Western blotting and immunohistochemistry were performed. The finding were as follows: 1. In parotid glands, clusterin was mildly increased and clearly expressed in the ductal cell under restraint stress immediately after application of the stress. 2. In parotid glands, clusterin was significantly decreased and slightly stained in the ductal cell under restraint stress 24 and 48 hours after experiment. 3. In parotid glands, clusterin was prominently increased again and densely stained in the ductal cell under restraint stress 72 hours after experiment.