The present study investigates the molecular details of how arsenic trioxide inhibits preadipocyte differentiation and examines the role of Akt/PKB in regulation of differentiation and apoptosis. Continual exposure of...The present study investigates the molecular details of how arsenic trioxide inhibits preadipocyte differentiation and examines the role of Akt/PKB in regulation of differentiation and apoptosis. Continual exposure of arsenic trioxide, at the clinic achievable dosage that does not induce apoptosis, suppressed 3T3-L1 cell differentiation into fat cells by inhibiting the expression of PPARγ and C/EBPα and disrupting the interaction between PPARγ and RXRα, which determines the programming of the adipogenic genes. Interestingly, if we treated the cells for 12 or 24 h and then withdrew arsenic trioxide, the cells were able to differentiate to the comparable levels of untreated cells as assayed by the activity of GAPDH, the biochemical marker of preadipocyte differentiation. Long term treatment blocked the differentiation and the activity of GAPDH could not recover to the comparable levels of untreated cells. Continual exposure of arsenic trioxide caused accumulation in G2/M phase and the accumulation of p21. We found that arsenic trioxide induced the expression and the phosphorylation of Akt/PKB and it inhibited the interaction between Akt/PKB and PPARγ . Akt/PKB inhibitor appears to block the arsenic trioxide suppression of differentiation. Our results suggested that Akt/PKB may play a role in suppression of apoptosis and negatively regulate preadipocyte differentiation.展开更多
Liposarcoma is the most common soft tissue sarcoma and accounts for 15%-20% of all mesenchymal malignancies. The tumor occurs most frequently in the limbs, retroperitoneum and rarely has a visceral location. We report...Liposarcoma is the most common soft tissue sarcoma and accounts for 15%-20% of all mesenchymal malignancies. The tumor occurs most frequently in the limbs, retroperitoneum and rarely has a visceral location. We report a case of a gastric liposarcoma in a male patient. A 68 years old male patient was admitted to hospital for abdominal discomfort and fullness lasting for a month. He reported rare episodes of vomiting. The CT examination revealed a large epigastric mass (8 cm x 4 cm) involving the lesser curvature of the stomach, in contact with the pancreas and gallbladder. Fatty areas within the mass were evident. A total gastrectomy together with cholecystectomy was performed. The histopathological diagnosis was a well differentiated liposarcoma. The patient did not undergo any adjuvant treatment, he is under close follow up and two years later he is disease free. We report this case due to the rarity of this tumor in the stomach (nine cases reported in the literature).展开更多
Objective: To explore the effects of thiazolidinediones(TZDs) pioglitazone on proliferation and differentiation of human preadipocytes. Methods:Omental adipose tissue biopsies were obtained from 15 patients who were u...Objective: To explore the effects of thiazolidinediones(TZDs) pioglitazone on proliferation and differentiation of human preadipocytes. Methods:Omental adipose tissue biopsies were obtained from 15 patients who were undergoing elective open-abdominal surgery. The primary culture and differentiated induction of human preadipocytes were performed, and the human preadipo-cytes were treated with pioglitazone at different concentrations at proper moments. Dynamic morphological changes of the human preadipocytes were observed, and their proliferation and differentiation were assessed with Colorimetric MTT Assay and Oil Red O Staining. Results:After 24 hours and 72 hours with pioglitazone, 0.1 μmol/L(μmol/ml) pioglitazone increased the MTT values of the human preadipocytes by 25.3% and 34.8%,respectively(P < 0.05), while 1 μmol/L pioglitazone by 27.4% and 26.6%(P < 0.05), compared with the control group without pioglitazone. The human preadipocytes with pioglitazone cumulated more adipose in the endochylema than those without pioglitazone obviously. 0.1 μmol/L pioglitazone increased the differentiation degree of the human preadipocytes differentiated for 8-10 days by 44.81% and 1 μmol/L pioglitazone by 53.76%(P < 0.05). Conclusion:Thiazolidinediones pioglitazone may significantly promote the proliferation and differentiation of the human omental preadipocytes.展开更多
Background Resistin, a newly discovered cysteine-rich hormone secreted mainly by adipose tissues, has been proposed to form a biochemical link between obesity and type 2 diabetes. However, the resistin receptor has no...Background Resistin, a newly discovered cysteine-rich hormone secreted mainly by adipose tissues, has been proposed to form a biochemical link between obesity and type 2 diabetes. However, the resistin receptor has not yet been identified. This study aimed to identify resistin binding proteins/receptor. Methods Three cDNA fragments with the same 11 bp 5’ sequence were found by screening a cDNA phage display library of rat multiple tissues. As the reading frames of the same 11 bp 5’ sequence were interrupted by a TGA stop codon, plaque lift assay was consequently used to prove the readthrough phenomenon. The stop codon in the same 11 bp 5’ sequence was replaced by tryptophan, and the binding activity of the coded peptide [AWIL, which was designated as resistin binding peptide (RBP)] with resistin was identified by the confocal microscopy technique and the affinity chromatography experiment. pDual GC-resistin and pDual GC-resistin binding peptide were co-transfected into 3T3-L1 cells to confirm the function of resistin binding peptide. Results Three cDNA fragments with the same 11 bp 5’ sequence were found. The TGA stop codon in reading frames of the same 11 bp 5’ sequence was proved to be readthroughed. The binding activity of RBP with resistin was consequently identified. The expression of the resistin binding peptide in 3T3-L1 preadipocytes expressing pDual GC-resistin significantly inhibited the adipogenic differentiation. Conclusion RBP could effectively rescue the promoted differentiation of resistin overxepressed 3T3-L1 preadipocyte.展开更多
基金This work is supported by grants from National Nature Science Foundation of China(No.30000083)Quan.CHEN's laboratory was supported by grants“Knowledge Innovation Key Project"(kscx2-sw-2010)of Chinese Academy of Sciences+1 种基金the National Basic Research Program of China(973 program project,No.2002CB5 13 100)National Fund for Outstanding Young Scholars from NSFC(30325013)awarded to Quan CHEN.
文摘The present study investigates the molecular details of how arsenic trioxide inhibits preadipocyte differentiation and examines the role of Akt/PKB in regulation of differentiation and apoptosis. Continual exposure of arsenic trioxide, at the clinic achievable dosage that does not induce apoptosis, suppressed 3T3-L1 cell differentiation into fat cells by inhibiting the expression of PPARγ and C/EBPα and disrupting the interaction between PPARγ and RXRα, which determines the programming of the adipogenic genes. Interestingly, if we treated the cells for 12 or 24 h and then withdrew arsenic trioxide, the cells were able to differentiate to the comparable levels of untreated cells as assayed by the activity of GAPDH, the biochemical marker of preadipocyte differentiation. Long term treatment blocked the differentiation and the activity of GAPDH could not recover to the comparable levels of untreated cells. Continual exposure of arsenic trioxide caused accumulation in G2/M phase and the accumulation of p21. We found that arsenic trioxide induced the expression and the phosphorylation of Akt/PKB and it inhibited the interaction between Akt/PKB and PPARγ . Akt/PKB inhibitor appears to block the arsenic trioxide suppression of differentiation. Our results suggested that Akt/PKB may play a role in suppression of apoptosis and negatively regulate preadipocyte differentiation.
文摘Liposarcoma is the most common soft tissue sarcoma and accounts for 15%-20% of all mesenchymal malignancies. The tumor occurs most frequently in the limbs, retroperitoneum and rarely has a visceral location. We report a case of a gastric liposarcoma in a male patient. A 68 years old male patient was admitted to hospital for abdominal discomfort and fullness lasting for a month. He reported rare episodes of vomiting. The CT examination revealed a large epigastric mass (8 cm x 4 cm) involving the lesser curvature of the stomach, in contact with the pancreas and gallbladder. Fatty areas within the mass were evident. A total gastrectomy together with cholecystectomy was performed. The histopathological diagnosis was a well differentiated liposarcoma. The patient did not undergo any adjuvant treatment, he is under close follow up and two years later he is disease free. We report this case due to the rarity of this tumor in the stomach (nine cases reported in the literature).
文摘Objective: To explore the effects of thiazolidinediones(TZDs) pioglitazone on proliferation and differentiation of human preadipocytes. Methods:Omental adipose tissue biopsies were obtained from 15 patients who were undergoing elective open-abdominal surgery. The primary culture and differentiated induction of human preadipocytes were performed, and the human preadipo-cytes were treated with pioglitazone at different concentrations at proper moments. Dynamic morphological changes of the human preadipocytes were observed, and their proliferation and differentiation were assessed with Colorimetric MTT Assay and Oil Red O Staining. Results:After 24 hours and 72 hours with pioglitazone, 0.1 μmol/L(μmol/ml) pioglitazone increased the MTT values of the human preadipocytes by 25.3% and 34.8%,respectively(P < 0.05), while 1 μmol/L pioglitazone by 27.4% and 26.6%(P < 0.05), compared with the control group without pioglitazone. The human preadipocytes with pioglitazone cumulated more adipose in the endochylema than those without pioglitazone obviously. 0.1 μmol/L pioglitazone increased the differentiation degree of the human preadipocytes differentiated for 8-10 days by 44.81% and 1 μmol/L pioglitazone by 53.76%(P < 0.05). Conclusion:Thiazolidinediones pioglitazone may significantly promote the proliferation and differentiation of the human omental preadipocytes.
基金This study was supported by grants from the National Natural Science Foundation of China (No. 30371502) the Natural Science Foundation of Jiangsu Province (No. BK2001120)Jiangsu Provincial Health Bureau (No. RC2002061).
文摘Background Resistin, a newly discovered cysteine-rich hormone secreted mainly by adipose tissues, has been proposed to form a biochemical link between obesity and type 2 diabetes. However, the resistin receptor has not yet been identified. This study aimed to identify resistin binding proteins/receptor. Methods Three cDNA fragments with the same 11 bp 5’ sequence were found by screening a cDNA phage display library of rat multiple tissues. As the reading frames of the same 11 bp 5’ sequence were interrupted by a TGA stop codon, plaque lift assay was consequently used to prove the readthrough phenomenon. The stop codon in the same 11 bp 5’ sequence was replaced by tryptophan, and the binding activity of the coded peptide [AWIL, which was designated as resistin binding peptide (RBP)] with resistin was identified by the confocal microscopy technique and the affinity chromatography experiment. pDual GC-resistin and pDual GC-resistin binding peptide were co-transfected into 3T3-L1 cells to confirm the function of resistin binding peptide. Results Three cDNA fragments with the same 11 bp 5’ sequence were found. The TGA stop codon in reading frames of the same 11 bp 5’ sequence was proved to be readthroughed. The binding activity of RBP with resistin was consequently identified. The expression of the resistin binding peptide in 3T3-L1 preadipocytes expressing pDual GC-resistin significantly inhibited the adipogenic differentiation. Conclusion RBP could effectively rescue the promoted differentiation of resistin overxepressed 3T3-L1 preadipocyte.