Biomedical subjects

Qian Jiang

Publications and source records attributed to Qian Jiang.

40 records · Page 3Linked to original sources

PubMed2003

Parkin is recruited to the centrosome in response to inhibition of proteasomes.

Parkin is a protein-ubiquitin E3 ligase linked to Parkinson's disease. Although several substrates of parkin have been identified, the subcellular location for parkin to recognize and ubiquitinate its targets is unclear. Here we report that parkin was accumulated in the centrosome when SH-SY5Y or transfected HEK293 cells were treated with the proteasome inhibitor lactacystin. The specific recruitment of parkin was dependent on concentration and duration of the treatment, and was accompanied by the centrosomal accumulation of ubiquitinated proteins and CDCrel-1, a substrate of parkin. The recruitment of parkin was apparently mediated through its binding to gamma-tubulin, which has been shown to accumulate in the centrosome in response to misfolded proteins. Furthermore, the effect was abrogated by the microtubule-depolymerizing drug colchicine or the microtubule-stabilizing drug taxol, which indicates that the intact microtubule network is required for the centrosomal recruitment of parkin. Taken together, our data suggest that the lactacystin-induced accumulation of parkin in the centrosome plays a significant role in the ubiquitination of misfolded substrates accumulated there. This process may provide a subcellular locale for parkin to ubiquitinate and degrade protein aggregates critically involved in the pathogenesis of Parkinson's disease.

3T3 Cells↗

PubMed2003

[Relationship between cytopenia and cytogenetic response in imatinib mesylate treated Ph-positive chronic myeloid leukemia in chronic phase patients].

OBJECTIVES: To evaluate the relationship between cytopenia and cytogenetic response in Imatinib mesylate treated Ph-positive chronic myeloid leukemia (CML) in chronic phase patients. METHODS: Fifty-four patients with Ph + CML in chronic phase received oral administration of Imatinib 400 or 600 mg once a day for 18 months. RESULTS: In the early phase of Imatinib treatment, rates of severe leukopenia (leukocyte < 2.0 x 10(9) L-1), anemia (hemoglobin < 100 g.L-1) and severe thrombocytopenia (platelet < 50 x 10(9) L-1) were 14.8%, 37.0% and 27.8%, respectively. Hemocytes recovered in most patients with continued therapy. Treatment was interrupted or dosage reduced in a few patients. The lower the hemoglobin and higher the platelet before the regime, the lower the nadir of leukocytes and hemoglobin counts during the treatment. The lower the platelet count before the regime, the lower the nadir of platelets during the treatment. Risk factors for severe leukopenia were thrombocytosis (> or = 500 x 10(9) L-1) and basophilia > or = 5% before the treatment. Risk factors for severe thrombocytopenia were thrombocytopenia (< 100 x 10(9) L-1) and basophilia > or = 5% before the treatment. During the 12-month treatment with Imatinib, the statistically significant lower probabilities of cytogenetic response were observed at all checked points in patients with severe leukopenia, at the end of 3 and 6 months in patients with anemia, at the end of 3 months in patients with severe thrombocytopenia. CONCLUSION: Cytopenia is a common side effect in patients with CML in chronic phase treated with Imatinib mesylate. Severe leukopenia is associated with a sustained lower major cytogenetic response, whereas anemia and severe thrombocytopenia influence more for the first 6 months.

Administration, Oral↗

PubMed2003

[Treatment of 54 chronic myelogenous leukemia with Gleevec].

OBJECTIVE: To evaluate the efficacy and safety of Gleevec (Imatinib) in the treatment of patients with Ph positive chronic myeloid leukemia in chronic phase (CML-CP). METHODS: A total of 54 CML-CP patients in whom previous therapy with interferon-alpha had been failed or untolerated, or relapsed after allogeneic stem cell transplantation (allo-SCT) were treated with 400 mg/d of oral Gleevec for 6 to 11 months. RESULT: Fifty-three patients being able to evaluate achieved complete hematological response within 7 to 28 days. Fifty-two (98%) of them remained in this situation at last follow-up. One patient relapsed after 7 months' treatment, and progressed to accelerated phase. Gleevec induced major cytogenetic response in 37 patients (70%) and complete cytogenetic response in 27 (51%). Twenty-nine of 37 patients (78%) achieved major cytogenetic response within 3 months. Grade 3 neutropenia or thrombocytopenia occurred in about 10% of patients, which were manageable or tolerated. Grade 3 or 4 nonhematologic adverse effects were infrequent. Only 1 patient (2%) discontinued treatment because of drug-related adverse events. CONCLUSIONS: Gleevec induced high rate of cytogenetic and hematologic responses in patients with CML-CP who failed in previous interferon therapy. The adverse effects were mild and manageable, or no need for treatment.

Adolescent↗

PubMed2002

Activation, involvement and nuclear translocation of c-Jun N-terminal protein kinase 1 and 2 in glutamate-induced apoptosis in cultured rat cortical neurons.

Previous studies showed that c-Jun N-terminal protein kinase 1 and 2 (JNK1&2) were activated in some cases of excitotoxicity. In the present study, activation, subcellular distribution, involvement and upstream regulation of JNK1&2 were investigated in glutamate-induced excitotoxicity in cultured rat cortical neurons. As indicated by Western immunoblot from whole cellular extracts, while JNK1&2 were not significantly changed, the activated JNK1&2 (diphosphorylated JNK1&2, p-JNK1&2), were rapidly increased at 15 min exposure to 50 microM glutamate and reverted to basal level at 12 h after exposure, followed by a significant increase of apoptotic-like cell death as detected by DAPI (a fluorescent DNA binding dye) staining at 9-18 h after exposure. Blockage of the increase of p-JNK1&2 with JNK1&2 antisense oligodeoxynucleotides significantly prevented the cell death. The increase of p-JNK1&2 was largely prevented by blockage of NMDA receptor (a subtype of glutamate receptor) or protein kinase C (PKC), and each blockage also largely prevented the cell death. Combined blockage of PKC and JNK1&2 had no additive protective effect against cell death. Immunocytochemistry study showed at 15 min of glutamate exposure a whole cellular but mainly nuclear increase of p-JNK1&2, together with mild plasma decrease but large nuclear increase of JNK1&2, all of which were also largely prevented by blockage of NMDA receptor or PKC. These results suggested that mainly downstream of NMDA receptor-PKC pathway JNK1&2 were activated, nuclear translocated and causally involved in the glutamate-induced excitotoxicity, possibly through a nuclear elevation of p-JNK1&2.

Animals↗