Effect of PAIP1 on the metastatic potential and prognostic significance in oral squamous cell carcinoma / 国际口腔科学杂志·英文版

Poly Adenylate Binding Protein Interacting protein 1 (PAIP1) plays a critical role in translation initiation and is associated with the several cancer types. However, its function and clinical significance have not yet been described in oral squamous cell carcinoma (OSCC) and its associated features like lymph node metastasis (LNM). Here, we used the data available from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) to analyze PAIP1 expression in oral cancer. The publicly available data suggests that PAIP1 mRNA and protein levels were increased in OSCC. The high PAIP1 expression was more evident in samples with advanced stage, LNM, and worse pattern of invasion. Moreover, the in vitro experiments revealed that PAIP1 knockdown attenuated colony forming, the aggressiveness of OSCC cell lines, decreasing MMP9 activity and SRC phosphorylation. Importantly, we found a correlation between PAIP1 and pSRC through the analysis of the IHC scores and CPTAC data in patient samples. Our findings suggest that PAIP1 could be an independent prognostic factor in OSCC with LNM and a suitable therapeutic target to improve OSCC patient outcomes.

Guanabenz Acetate Induces Endoplasmic Reticulum Stress–Related Cell Death in Hepatocellular Carcinoma Cells

BACKGROUND: Development of chemotherapeutics for the treatment of advanced hepatocellular carcinoma (HCC) has been lagging. Screening of candidate therapeutic agents by using patient-derived preclinical models may facilitate drug discovery for HCC patients. METHODS: Four primary cultured HCC cells from surgically resected tumor tissues and six HCC cell lines were used for high-throughput screening of 252 drugs from the Prestwick Chemical Library. The efficacy and mechanisms of action of the candidate anti-cancer drug were analyzed via cell viability, cell cycle assays, and western blotting. RESULTS: Guanabenz acetate, which has been used as an antihypertensive drug, was screened as a candidate anti-cancer agent for HCC through a drug sensitivity assay by using the primary cultured HCC cells and HCC cell lines. Guanabenz acetate reduced HCC cell viability through apoptosis and autophagy. This occurred via inhibition of growth arrest and DNA damage-inducible protein 34, increased phosphorylation of eukaryotic initiation factor 2α, increased activating transcription factor 4, and cell cycle arrest. CONCLUSIONS: Guanabenz acetate induces endoplasmic reticulum stress–related cell death in HCC and may be repositioned as an anti-cancer therapeutic agent for HCC patients.

Sarcopenia: Ammonia metabolism and hepatic encephalopathy

Sarcopenia (loss of muscle mass and/or strength) frequently complicates liver cirrhosis and adversely affects the quality of life; cirrhosis related liver decompensation and significantly decreases wait-list and post-liver transplantation survival. The main therapeutic strategies to improve or reverse sarcopenia include dietary interventions (supplemental calorie and protein intake), increased physical activity (supervised resistance and endurance exercises), hormonal therapy (testosterone), and ammonia lowering agents (L-ornithine L-aspartate, branch chain amino acids) as well as mechanistic approaches that target underlying molecular and metabolic abnormalities. Besides other factors, hyperammonemia has recently gained attention and increase sarcopenia by various mechanisms including increased expression of myostatin, increased phosphorylation of eukaryotic initiation factor 2a, cataplerosis of α ketoglutarate, mitochondrial dysfunction, increased reactive oxygen species that decrease protein synthesis and increased autophagy-mediated proteolysis. Sarcopenia contributes to frailty and increases the risk of minimal and overt hepatic encephalopathy.

Inhibition of ER Stress by 2-Aminopurine Treatment Modulates Cardiomyopathy in a Murine Chronic Chagas Disease Model

Trypanosoma cruzi infection results in debilitating cardiomyopathy, which is a major cause of mortality and morbidity in the endemic regions of Chagas disease (CD). The pathogenesis of Chagasic cardiomyopathy (CCM) has been intensely studied as a chronic inflammatory disease until recent observations reporting the role of cardio-metabolic dysfunctions. In particular, we demonstrated accumulation of lipid droplets and impaired cardiac lipid metabolism in the hearts of cardiomyopathic mice and patients, and their association with impaired mitochondrial functions and endoplasmic reticulum (ER) stress in CD mice. In the present study, we examined whether treating infected mice with an ER stress inhibitor can modify the pathogenesis of cardiomyopathy during chronic stages of infection. T. cruzi infected mice were treated with an ER stress inhibitor 2-Aminopurine (2AP) during the indeterminate stage and evaluated for cardiac pathophysiology during the subsequent chronic stage. Our study demonstrates that inhibition of ER stress improves cardiac pathology caused by T. cruzi infection by reducing ER stress and downstream signaling of phosphorylated eukaryotic initiation factor (P-elF2α) in the hearts of chronically infected mice. Importantly, cardiac ultrasound imaging showed amelioration of ventricular enlargement, suggesting that inhibition of ER stress may be a valuable strategy to combat the progression of cardiomyopathy in Chagas patients.

Overexpression of eukaryotic initiation factor 5A (eIF5A) affects susceptibility to benznidazole in Trypanosoma cruzi populations

Eukaryotic initiation factor 5A (eIF5A) is a conserved protein with an essential role in translation elongation. Using one and two-dimensional western blotting, we showed that the eIF5A protein level was 2-fold lower in benznidazole (BZ)-resistant (BZR and 17LER) Trypanosoma cruzi populations than in their respective susceptible counterparts (BZS and 17WTS). To confirm the role of eIF5A in BZ resistance, we transfected BZS and 17WTS with the wild-type eIF5A or mutant eIF5A-S2A (in which serine 2 was replaced by alanine). Upon overexpressing eIF5A, both susceptible lines became approximately 3- and 5-fold more sensitive to BZ. In contrast, the eIF5A-S2A mutant did not alter its susceptibility to BZ. These data suggest that BZ resistance might arise from either decreasing the translation of proteins that require eIF5A, or as a consequence of differential levels of precursors for the hypusination reactions (e.g., spermidine and trypanothione), both of which alter BZ's effects in the parasite.

Pioglitazone Attenuates Palmitate-Induced Inflammation and Endoplasmic Reticulum Stress in Pancreatic β-Cells

BACKGROUND: The nuclear receptor peroxisome proliferator-activator gamma (PPARγ) is a useful therapeutic target for obesity and diabetes, but its role in protecting β-cell function and viability is unclear. METHODS: To identify the potential functions of PPARγ in β-cells, we treated mouse insulinoma 6 (MIN6) cells with the PPARγ agonist pioglitazone in conditions of lipotoxicity, endoplasmic reticulum (ER) stress, and inflammation. RESULTS: Palmitate-treated cells incubated with pioglitazone exhibited significant improvements in glucose-stimulated insulin secretion and the repression of apoptosis, as shown by decreased caspase-3 cleavage and poly (adenosine diphosphate [ADP]-ribose) polymerase activity. Pioglitazone also reversed the palmitate-induced expression of inflammatory cytokines (tumor necrosis factor α, interleukin 6 [IL-6], and IL-1β) and ER stress markers (phosphor-eukaryotic translation initiation factor 2α, glucose-regulated protein 78 [GRP78], cleaved-activating transcription factor 6 [ATF6], and C/EBP homologous protein [CHOP]), and pioglitazone significantly attenuated inflammation and ER stress in lipopolysaccharide- or tunicamycin-treated MIN6 cells. The protective effect of pioglitazone was also tested in pancreatic islets from high-fat-fed KK-Ay mice administered 0.02% (wt/wt) pioglitazone or vehicle for 6 weeks. Pioglitazone remarkably reduced the expression of ATF6α, GRP78, and monocyte chemoattractant protein-1, prevented α-cell infiltration into the pancreatic islets, and upregulated glucose transporter 2 (Glut2) expression in β-cells. Moreover, the preservation of β-cells by pioglitazone was accompanied by a significant reduction of blood glucose levels. CONCLUSION: Altogether, these results support the proposal that PPARγ agonists not only suppress insulin resistance, but also prevent β-cell impairment via protection against ER stress and inflammation. The activation of PPARγ might be a new therapeutic approach for improving β-cell survival and insulin secretion in patients with diabetes mellitus

Inhibition of Mast Cell Function and Proliferation by mTOR Activator MHY1485

Mast cells integrate innate and adaptive immunity and are implicated in pathophysiological conditions, including allergy, asthma, and anaphylaxis. Cross-linking of the high-affinity IgE receptor (FcεRI) initiates diverse signal transduction pathways and induces release of proinflammatory mediators by mast cells. In this study, we demonstrated that hyperactivation of mechanistic target of rapamycin (mTOR) signaling using the mTOR activator MHY1485 suppresses FcεRI-mediated mast cell degranulation and cytokine secretion. MHY1485 treatment increased ribosomal protein S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation, which are downstream targets of mTOR complex 1 (mTORC1), but decreased phosphorylation of Akt on mTOR complex 2 (mTORC2) target site serine 473. In addition, this activator decreased β-hexosaminidase, IL-6, and tumor necrosis factor α (TNF-α) release in murine bone marrow-derived mast cells (BMMCs) after FcεRI stimulation. Furthermore, MHY1485-treated BMMCs showed significantly decreased proliferation when cultured with IL-3. These findings suggested hyperactivation of mTORC1 as a therapeutic strategy for mast cell-related diseases.

The lipid droplet: A conserved cellular organelle

The lipid droplet (LD) is a unique multi-functional organelle that contains a neutral lipid core covered with a phospholipid monolayer membrane. The LDs have been found in almost all organisms from bacteria to humans with similar shape. Several conserved functions of LDs have been revealed by recent studies, including lipid metabolism and trafficking, as well as nucleic acid binding and protection. We summarized these findings and proposed a hypothesis that the LD is a conserved organelle.

Eukaryotic Translation Initiation Factor 3a (eIF3a) Promotes Cell Proliferation and Motility in Pancreatic Cancer

Identifying a target molecule that is crucially involved in pancreatic tumor growth and metastasis is necessary in developing an effective treatment. The study aimed to investigate the role of the eukaryotic translation initiation factor 3a (eIF3a) in the cell proliferation and motility in pancreatic cancer. Our data showed that the expression of eIF3a was upregulated in pancreatic ductal adenocarcinoma as compared with its expression in normal pancreatic tissues. Knockdown of eIF3a by a specific shRNA caused significant decreases in cell proliferation and clonogenic abilities in pancreatic cancer SW1990 and Capan-1 cells. Consistently, the pancreatic cancer cell growth rates were also impaired in xenotransplanted mice. Moreover, wound-healing assay showed that depletion of eIF3a significantly slowed down the wound recovery processes in SW1990 and Capan-1 cells. Transwell migration and invasion assays further showed that cell migration and invasion abilities were significantly inhibited by knockdown of eIF3a in SW1990 and Capan-1 cells. Statistical analysis of eIF3a expression in 140 cases of pancreatic ductal adenocarcinoma samples revealed that eIF3a expression was significantly associated with tumor metastasis and TNM staging. These analyses suggest that eIF3a contributes to cell proliferation and motility in pancreatic ductal adenocarcinoma.

Non-negligible Occurrence of Errors in Gender Description in Public Data Sets

Due to advances in omics technologies, numerous genome-wide studies on human samples have been published, and most of the omics data with the associated clinical information are available in public repositories, such as Gene Expression Omnibus and ArrayExpress. While analyzing several public datasets, we observed that errors in gender information occur quite often in public datasets. When we analyzed the gender description and the methylation patterns of gender-specific probes (glucose-6-phosphate dehydrogenase [G6PD], ephrin-B1 [EFNB1], and testis specific protein, Y-linked 2 [TSPY2]) in 5,611 samples produced using Infinium 450K HumanMethylation arrays, we found that 19 samples from 7 datasets were erroneously described. We also analyzed 1,819 samples produced using the Affymetrix U133Plus2 array using several gender-specific genes (X (inactive)-specific transcript [XIST], eukaryotic translation initiation factor 1A, Y-linked [EIF1AY], and DEAD [Asp-Glu-Ala-Asp] box polypeptide 3, Y-linked [DDDX3Y]) and found that 40 samples from 3 datasets were erroneously described. We suggest that the users of public datasets should not expect that the data are error-free and, whenever possible, that they should check the consistency of the data.

Process of Hypertrophic Scar Formation: Expression of Eukaryotic Initiation Factor 6 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypertrophic scar is one of the most common complications and often causes the disfigurement or deformity in burn or trauma patients. Therapeutic methods on hypertrophic scar treatment have limitations due to the poor understanding of mechanisms of hypertrophic scar formation. To throw light on the molecular mechanism of hypertrophic scar formation will definitely improve the outcome of the treatment. This study aimed to illustrate the negative role of eukaryotic initiation factor 6 (eIF6) in the process of human hypertrophic scar formation, and provide a possible indicator of hypertrophic scar treatment and a potential target molecule for hypertrophic scar.</p><p><b>METHODS</b>In the present study, we investigated the protein expression of eIF6 in the human hypertrophic scar of different periods by immunohistochemistry and Western blot analysis.</p><p><b>RESULTS</b>In the hypertrophic scar tissue, eIF6 expression was significantly decreased and absent in the basal layer of epidermis in the early period, and increased slowly and began to appear in the basal layer of epidermis by the scar formation time.</p><p><b>CONCLUSIONS</b>This study confirmed that eIF6 expression was significantly related to the development of hypertrophic scar, and the eIF6 may be a target molecule for hypertrophic scar control or could be an indicator of the outcomes for other treatment modalities.</p>

Effects of eukaryotic translation initiation factor 5A2 down-regulation by small interfering RNA on aggressiveness of MKN28 human / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the effects of eukaryotic translation initiation factor 5A2 (EIF5A2) down-regulation by small interfering RNA (siRNA) on aggressiveness of human gastric cancer cell and its potential mechanisms.</p><p><b>METHODS</b>The expressions of EIF5A2 in human gastric cancer cell lines (MKN28 and HGC27) and immortalized gastric mucosal epithelial cells (GES-1) were measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. EIF5A2 gene in MKN28 cells was silenced by RNA interference and the inhibitory effect was evaluated by both qRT-PCR and Western blotting. Cell proliferation was assessed by CCK-8 assay. Cell migration and invasion were assessed by Transwell assay. The possible downstream targets of EIF5A2, such as CyclinD1, CyclinD3, matrix metallopeptidase-9 (MMP-9), E-cadherin, vimintin, C-myc, and metastasis-associated protein 1 (MTA1) expression levels, were examined by Western blotting.</p><p><b>RESULTS</b>High expressions of EIF5A2 were found in MKN28 cells and human gastric adenocarcinoma tissues. Both EIF5A2 mRNA and protein expression in MKN28 cells were significantly down-regulated by siRNA#1 and siRNA#2, especially siRNA#1. Knockdown of EIF5A2 caused an apparent suppression of MKN28 cell proliferation (all P<0.01), migration (P<0.001), and invasion (P<0.001). After the knockdown of EIF5A2 in MKN28 cells, E-cadherin levels were upregulated, whereas vimentin, Cyclin D1, Cyclin D3, C-myc and MTA1 levels were downregulated.</p><p><b>CONCLUSION</b>Knockdown of EIF5A2 may inhibit MKN28 cell proliferation by downregulating the CyclinD1 and CyclinD3 and suppressing the cell migration and invasion by inhibiting MTA1, C-myc and epithelial-mesenchymal transition.</p>

Expression of eukaryotic translation initiation factor 5A2 in pancreatic adenocarcinoma and its correlation with the prognosis / 中国医学科学院学报

<p><b>OBJECTIVE</b>To detect the expression of eukaryotic translation initiation factor 5A2(EIF5A2) in pancreatic adenocarcinoma and its correlation with the clinicopathological characteristics and prognosis.</p><p><b>METHODS</b>A total of 73 patients who were treated in our hospital from March 2007 to December 2008 were enrolled in this study. The expression of EIF5A2 in the surgical samples was detected using immunohistochemical staining. Complete clinicopathological data were obtained from all the patients. The potential correlation between EIF5A2 expression and the clinicopathological features, particularly its role in prognosis, were analyzed.</p><p><b>RESULTS</b>Of these 73 patients, 43 had a high EIF5A2 expression. EIF5A2 expression was significantly correlated with the pathological T stage(P<0.001), N stage(P=0.004), M stage(P=0.039), and TNM stage(P=0.005). Kaplan-Meier method demonstrated that the survival was significantly longer in the low EIF5A2 expression group than in the high EIF5A2 expression group(P=0.003). Cox's hazard model showed EIF5A2 was a significant predictor of overall survival in patients with pancreatic adenocarcinoma.</p><p><b>CONCLUSION</b>EIF5A2 may be a potential predictor of the poor prognosis in patients with pancreatic adenocarcinoma.</p>

Differential gene expression pattern in brains of acrylamide-administered mice / 대한수의학회지

The present study was performed to evaluate the relationship between the neurotoxicity of acrylamide and the differential gene expression pattern in mice. Both locomotor test and rota-rod test showed that the group treated with higher than 30 mg/kg/day of acrylamide caused impaired motor activity in mice. Based on cDNA microarray analysis of mouse brain, myelin basic protein gene, kinesin family member 5B gene, and fibroblast growth factor (FGF) 1 and its receptor genes were down-regulated by acrylamide. The genes are known to be essential for neurofilament synthesis, axonal transport, and neuro-protection, respectively. Interestingly, both FGF 1 and its receptor genes were down-regulated. Genes involved in nucleic acid binding such as AU RNA binding protein/enoyl-coA hydratase, translation initiation factor (TIF) 2 alpha kinase 4, activating transcription factor 2, and U2AF 1 related sequence 1 genes were down-regulated. More interesting finding was that genes of both catalytic and regulatory subunit of protein phosphatases which are important for signal transduction pathways were down-regulated. Here, we propose that acrylamide induces neurotoxicity by regulation of genes associated with neurofilament synthesis, axonal transport, neuro-protection, and signal transduction pathways.

RNA Granules and Stress Granules in Virus Systems

Viruses initiate a number of cellular stress responses and modulate gene regulation and compartmentalization of RNA upon infection to be successful parasites. Virus infections may induce or impair stress granule (SG) formation to maximize replication efficiency. SGs and processing bodies (PBs) are the RNA granules, which contain translationally inactive pool of transcripts as the mRNA silencing foci. PBs and SGs, the highly conserved macromolecular aggregates, can release mRNAs to allow their translations. Unlike constitutively existing PBs that can respond to stimuli and affect mRNA translation and decay, SGs are specifically induced upon cellular stress and can triggers a global translational silencing by several pathways, including phosphorylation of the key translation initiation factor eIF2alpha, tRNA cleavage, and sequestration of cellular components and so on. The dynamics of PBs and SGs are regulated by several signaling pathways, including histone deacetylase 6, and depend on microfilaments and microtubules, and the cognate molecular motors myosin, dynein, and kinesin. SGs share features with aggresomes and related aggregates of unfolded proteins and may play a role in the pathology. The recent advances in understanding the relationship between viruses and mRNA stress granules are summarized.

Post-traumatic Intramuscular Hemangioma of the Chest Wall

Intramuscular hemangioma originated in chest wall is a rare benign tumor, with no relevant reports in Korea. In most cases, the tumor is discovered before the age of 30 years and it is reported that trauma operates as the initiation factor. It is essential to concern the clinical suspicion and conduct a CT scan for diagnosis. The principle of treatment is surgical excision with clear resection margin. The authors of this study report a case of surgical excision for post-traumatic intramuscular hemangioma of the chest wall with review of literature.

The Effects of Glyburide on Apoptosis and Endoplasmic Reticulum Stress in INS-1 Cells in a Glucolipotoxic Condition

BACKGROUND: beta-cell death due to endoplasmic reticulum (ER) stress has been regarded as an important pathogenic component of type 2 diabetes. The possibility has been suggested that sulfonylurea, currently being used as one of the main oral hypoglycemic agents of type 2 diabetes, increases ER stress, which could lead to sulfonylurea failure. The authors of the present study examined ER stress of beta-cells in a glucolipotoxic condition using glyburide (GB) in an environment mimicking type 2 diabetes. METHODS: Apoptosis was induced by adding various concentrations of GB (0.001 to 200 microM) to a glucolipotoxic condition using 33 mM glucose, and the effects of varied concentrations of palmitate were evaluated via annexin V staining. The markers of ER stress and pro-apoptotic markers were assessed by Western blotting and semi-quantitative reverse transcription-polymerase chain reaction. Additionally, the anti-apoptotic markers were evaluated. RESULTS: Addition of any concentration of GB in 150 microM palmitate and 33 mM glucose did not increase apoptosis. The expression of phosphorylated eukaryotic initiation factor (eIF-2alpha) was increased and cleaved caspase 3 was decreased by adding GB to a glucolipotoxic condition. However, other ER stress-associated markers such as Bip-1, X-box binding protein-1, ATF-4 and C/EBP-homologous protein transcription factor and anti-apoptotic markers phosphor-p85 phosphatidylinositol 3-kinase and phosphorylation of Akt did not change significantly. CONCLUSION: GB did not show further deleterious effects on the degree of apoptosis or ER stress of INS-1 cells in a glucolipotoxic condition. Increased phosphorylation of eIF-2alpha may attenuate ER stress for adaptation to increased ER protein load.

4-phenylbutyric Acid Regulates Collagen Synthesis and Secretion Induced by High Concentrations of Glucose in Human Gingival Fibroblasts

High glucose leads to physio/pathological alterations in diabetes patients. We investigated collagen production in human gingival cells that were cultured in high concentrations of glucose. Collagen synthesis and secretion were increased when the cells were exposed to high concentrations of glucose. We examined endoplasmic reticulum (ER) stress response because glucose metabolism is related to ER functional status. An ER stress response including the expression of glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), inositol requiring enzyme alpha (IRE-1alpha) and phosphoreukaryotic initiation factor alpha (p-eIF-2alpha) was activated in the presence of high glucose. Activating transcription factor 4 (ATF-4), a downstream protein of p-eIF-2alpha as well as a transcription factor for collagen, was also phosphorylated and translocalized into the nucleus. The chemical chaperone 4-PBA inhibited the ER stress response and ATF-4 phosphorylation as well as nuclear translocation. Our results suggest that high concentrations of glucose-induced collagen are linked to ER stress and the associated phosphorylation and nuclear translocation of ATF-4.

Proteomic Analysis of Hepatic Ischemia and Reperfusion Injury in Mice / 한국실험동물학회지

Hepatic ischemia/reperfusion (I/R) injury is an inevitable consequence during liver surgery. I/R injury induces serious hepatic dysfunction and failure. In this study, we identified proteins that were differentially expressed between sham and I/R injured livers. Animals were subjected to hepatic ischemia for 1 hr and were sacrificed at 3hr after reperfusion. Serum ALT and AST levels were significantly increased in I/R-operated animals compared to those of sham-operated animals. Ischemic hepatic lobes of I/R-operated animals showed the hepatic lesion with unclear condensation and sinusoidal congestion. Proteins from hepatic tissue were separated using two dimensional gel electrophosresis. Protein spots with a greater than 2.5-fold change in intensity were identified by mass spectrometry. Among these proteins, glutaredoxin-3, peroxiredoxin-3, glyoxalase I, spermidine synthase, dynamin-1-like protein, annexin A4, eukaryotic initiation factor 3, eukaryotic initiation factor 4A-I, 26S proteasome, proteasome alpha 1, and proteasome beta 4 levels were significantly decreased in I/R-operated animals compared to those of sham-operated animals. These proteins are related to protein synthesis, cellular growth and stabilization, anti-oxidant action. Moreover, Western blot analysis confirmed that dynamin-1-like protein levels were decreased in I/R-operated animals. Our results suggest that hepatic I/R induces the hepatic cells damage by regulation of several proteins.

Proteomic Changes in the Female Rat Bladder Tissue following Bilateral Oophorectomy

PURPOSE: To explore the effect of bilateral oophorectomy on the several proteins of female rat bladder via a proteomic approach. MATERIALS AND METHODS: A total of 20 female Sprague-Dawley rats were obtained at 8 weeks of age and were divided randomly into 3 groups: a control groups underwent sham operation and bladders were excised 4 weeks and 8 weeks after operation each. Other two groups underwent bilateral oophorectomy and bladders were excised 4 weeks (group 1) and 8 weeks (group 2) after operation each, too. Each group has 5 rats. Conventional proteomics was conducted via high resolution 2-D gel electrophoresis, followed by image analysis and protein identification through mass spectrometry. RESULTS: Bladder weights were reduced significantly in group 2 as compared with the 8-week control group. A comparison of the bladders of the oophorectomy group subjects with those of the control group subjects demonstrated that the expressions of 11 proteins were altered Eukaryotic translation initiation factor 5A (elF-5A), chaperone grp 75 precursor, actin-depolymerizing factor, contrapsin-like inhibitor 1 precursor, guanine deaminase, actin, peroxiredoxin 2, phosphatidylethanolamine, putative protein kinase, Keratin complex 2 and Enol protein. CONCLUSION: The roles of 11 proteins are variable. A part of these proteins have a role of cellular apoptosis, acute inflammation, and muscle contraction. It seems that these changes of proteins have an influence on bladder functions and LUTS.