Biomedical subjects

J B Lin

Publications and source records attributed to J B Lin.

13 recordsLinked to original sources

PubMed2006

Upregulation of endothelial heme oxygenase-1 expression through the activation of the JNK pathway by sublethal concentrations of acrolein.

Acrolein is a highly electrophilic alpha,beta-unsaturated aldehyde that is present in cigarette smoke. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme activated by various such electrophilic compounds. In this study, the regulatory effects of acrolein upon the expression of HO-1 were investigated in endothelial cells (ECs). We demonstrate that acrolein induces the elevation of HO-1 protein levels, and subsequent enzyme activity, at non-cytotoxic concentrations. An additional alpha,beta-unsaturated aldehyde, cinnamaldehyde, was also found to increase HO-1 expression and have less cytotoxicity than acrolein. Moreover, acrolein-mediated HO-1 induction is abrogated in the presence of actinomycin D and cycloheximide. Nrf2 is a transcription factor involved in the induction of HO-1 through an antioxidant response element (ARE) in the promoter region of the HO-1 gene. We show that acrolein induces Nrf2 translocation and ARE-luciferase reporter activity. Acrolein was also found to induce the production of both superoxide and H2O2 at levels greater than 100 microM. However, with the exception of NAC, no antioxidant generated any effect upon acrolein-dependent HO-1 expression in ECs. Our present findings suggest that reactive oxygen species (ROS) may not be a major modulator for HO-1 induction. Using buthionine sulfoximine to deplete the intracellular GSH levels further enhanced the effects of acrolein. We also found that cellular GSH level was rapidly reduced after both 10 and 100 microM acrolein treatment. However, after 6 h of exposure to ECs, only 10 microM acrolein treatment increases GSH level. In addition, only the JNK inhibitor SP600125 and tyrosine kinase inhibitor genistein had any significant inhibitory impact upon the upregulation of HO-1 by acrolein. Pretreatment with a range of other PI3 kinase inhibitors, including wortmannin and LY294002, showed no effects. Hence, we show in our current experiments that a sublethal concentration of acrolein is in fact a novel HO-1 inducer, and we further identify the principal underlying mechanisms involved in this process.

Acrolein↗

PubMed2005

Upregulation of heme oxygenase-1 by Epigallocatechin-3-gallate via the phosphatidylinositol 3-kinase/Akt and ERK pathways.

Heme oxygenase-1 (HO-1) is a cytoprotective enzyme activated by various phytochemicals and we examined the ability of Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, to upregulate HO-1 expression in endothelial cells (ECs). We demonstrate that EGCG induces HO-1 expression in a concentration- and time-dependent manner. Furthermore, EGCG-mediated HO-1 induction was abrogated in the presence of actinomycin D and cycloheximide, indicating that this upregulation of HO-1 occurred at the transcriptional level. EGCG also upregulates Nrf2 levels in nuclear extracts and increases ARE-luciferase activity. Furthermore, EGCG is the most potent inducer of HO-1 expression of the different green tea constituents that we analyzed, but had no detectable cytotoxic effects over the 25-100 microM dosage range. The inhibition of intracellular ROS production by N-acetylcysteine (NAC), glutathione (GSH), superoxide dismutase (SOD), catalase and the mitochondrial complex I inhibitor, rotenone, results in a decrease in EGCG-dependent HO-1 expression. In addition, we determined that tyrosine kinase is involved in EGCG induction of HO-1 as this is abrogated by genistein. ECs treated with EGCG exhibit activation of Akt and ERK1/2. In addition, pharmacological inhibitors of phosphatidylinositol 3-kinase and MEK1/2, which are upstream of Akt and ERK1/2, respectively, attenuate EGCG-induced HO-1 expression. On the other hand, pretreatment of these cells with EGCG exerts significant cytoprotective effects against H2O2, suggesting that the induction of HO-1 is an important component in the protection against oxidative stress. Hence, EGCG is a novel phytochemical inducer of HO-1 expression and we further identify the principal underlying mechanisms involved in this process.

Animals↗

PubMed2000

Elevated topoisomerase I activity in cervical cancer as a target for chemoradiation therapy.

OBJECTIVE: The aim of this study was to determine whether the activity of topoisomerase I (topo I), the target of the anti-neoplastic drug camptothecin (CPT), is elevated in cervical cancer and whether CPT can radiosensitize cervical tumors. METHODS: The topo I activity of 11 normal cervix and 30 cervical carcinoma tumors was assayed by measuring the relaxation of supercoiled DNA. Subconfluent or postconfluent CaSki human cervical carcinoma cells were exposed to CPT (1-5000 ng/ml) and immediately X-irradiated (0-800 cGy). Cell survival was determined by clonogenic assay. RESULTS: Mean topo I activity in cervical cancer (3.0 +/- 0.06 h(-1)) was significantly greater than in normal cervix tissue (0.29 +/- 0.06 h(-1)). Stage 3 and 4 cervical carcinoma specimens displayed a trend of greater topo I activity (5.88 +/- 3.7 h(-1)) than stage 1 and 2 tumors (2.57 +/- 0.47 h(-1)). No correlation between topo I protein levels and catalytic activity was found. Combined treatment of subconfluent CaSki cells with CPT and ionizing radiation resulted in additive killing of cells. Combined treatment of postconfluent CaSki cells with low doses of radiation (200 and 400 cGy) and 1 or 10 ng/ml CPT for 2 or 48 h produced significant cytotoxicity compared to CPT or radiation alone, which were ineffective at these doses. CONCLUSIONS: Topo I activity is elevated in cervical cancer compared to normal cervix. The radiosensitivity of noncycling cells within cervical tumors may be increased by simultaneous treatment with low doses of CPT or other topo I inhibitors.

Antineoplastic Agents, Phytogenic↗

PubMed1995

In situ hybridization to chromosomes stabilized in gel microdrops.

Conventional chromosome in situ hybridization procedures rely on fixation to glass slides followed by microscopic evaluation. This report describes the development of a microdrop in situ hybridization to chromosomes in suspension. Chromosomes encapsulated in gel microdrops (GMDs) composed of an agarose matrix withstood stringent hybridization and denaturation conditions. Because of the increased stability, hybridization to encapsulated chromosomes was detected by flow cytometry as well as conventional microscopy. Thus, the MISH method offers a means for chromosome hybridization without slides and may enable identification and isolation of chromosome using hybridization rather than nucleic acid binding dyes.

3T3 Cells↗

PubMed1989

Waldenström's macroglobulinemia with unilateral massive pleural effusion: report of a case.

One rare case of Waldenström's macroglobulinemia with massive right-sided pleural effusion is reported. A 66-year-old woman was admitted to our hospital because of exertional dyspnea and chronic cough of three months' duration. Chest X-ray examination showed massive right-sided pleural effusion. Routine blood examination revealed severe anemia. Sternal bone marrow aspirate revealed a hypercellular marrow with replacement of 50% of the normal hematopoietic cells by a spectrum of lymphoid cells, including small lymphocytes, a few plasma-cytoid lymphocytes and immature plasma cells. The diagnosis was confirmed by serum protein electrophoresis and immunoglobulin assay. The effect of chemotherapy was satisfactory in the first two years as pleural effusion subsided completely and the marrow returned to near normal. But, the response was poor during the last 6 months. She died about 4 years after her first admission.

Aged↗

PubMed1989

Gastric xanthelasma.

Gastric xanthelasmas are macroscopically well demarcated yellow or yellow-white plaques, and microscopically composed of typical foamy macrophages. Of 3870 patients who underwent upper gastrointestinal panendoscopic examinations, 30 (0.8%) were found to have gastric xanthelasma. A moderate predominance of males over females (M:F = 3.3:1) was noted. The age ranged between 21 and 69 years (mean 46.7). Frequency peaked in those from 40 to 60 years of age (53.3%). Single lesions were found in 26 patients and multiple in 4, with diameters of 1-6 mm, nearly 66.7% of which were 2-3 mm. Gastric xanthelasmas are most frequently found in the antrum (67.8%), especially along the lesser curvature. Associated chronic gastritis in the xanthelasma surrounding mucosa was found in the 30 patients and intestinal metaplasia in 4 (13.3%). The cause of gastric xanthelasma is unknown, but chronic gastritis may be the most plausible etiologic factor.

Adult↗

PubMed1985