Yang K.,Guangzhou University |
Yang K.,Johns Hopkins University |
Lu W.,Guangzhou University |
Lu W.,Johns Hopkins University |
And 9 more authors.
American Journal of Respiratory Cell and Molecular Biology | Year: 2015
Our previous publication demonstrated that peroxisome proliferator-activated receptor g (PPARg) inhibits the pathogenesis of chronic hypoxia (CH)-induced pulmonary hypertension by targeting store-operated calcium entry (SOCE) in rat distal pulmonary arterial smooth muscle cells (PASMCs). In this study, we aim to determine the role of a membrane scaffolding protein, caveolin-1, during the suppressive process ofPPARg on SOCE. Adult (6-8 weeks) male Wistar rats (200-250 g) were exposed to CH (10% O2) for 21 days to establish CH-induced pulmonary hypertension. Primary cultured rat distal PASMCs were applied for the molecular biological experiments. First, hypoxic exposure led to 2.5-fold and 1-fold increases of caveolin-1 protein expression in the distal pulmonary arteries and PASMCs, respectively. Second, effective knockdown of caveolin-1 significantly reduced hypoxia-induced SOCE for 58.2% and 41.5%, measured by Mn21 quenching and extracellular Ca21 restoration experiments, respectively. These results suggested that caveolin-1 acts as a crucial regulator of SOCE, and hypoxia-up-regulated caveolin-1 largely accounts for hypoxia-elevated SOCE in PASMCs. Then, by using a high-potency PPARg agonist, GW1929, we detected that PPARg activation inhibited SOCE and caveolin-1 protein for 62.5% and 59.8% under hypoxia, respectively, suggesting that caveolin-1 also acts as a key target during the suppressive process of PPARg on SOCE in PASMCs. Moreover, by using effective small interfering RNAs against PPARg and caveolin-1, and PPARg antagonist, T0070907, we observed that PPARg plays an inhibitory role on caveolin-1 protein by promoting its lysosomal degradation, without affecting the messenger RNA level. PPARg inhibits SOCE, at least partially, by suppressing cellular caveolin-1 protein in PASMCs. © Copyright 2015 by the American Thoracic Society. Source
Yang J.,Renmin University of China |
Zhang Y.,Peoples Hospital of Inner Mongolia |
Zhao S.,Inner Mongolia University |
Zhang Z.,Inner Mongolia University |
And 3 more authors.
Molecular Medicine Reports | Year: 2015
Functional defects in heat shock proteins (HSPs), e.g. Hsp70, have been reported to have a key role in Parkinson's disease (PD). Overexpressed Hsp70 re-folds aggregated a-synuclein to generate the non-toxic and non-aggregated form. Thus, Hsp70 is a well-defined therapeutic target, and Hsp70 promotion is an efficient strategy to prevent or even reverse the a-synuclein-induced toxicity in PD. The present study investigated the promotion of Hsp70 expression in SH-SY5Y neuroblastoma cells by glutamine (Gln), which has recently been recognized to induce Hsp70 expression. Furthermore, the role of heat shock factor (HSF)-1 in the Gln-mediated upregulation of Hsp70 expression was investigated. In addition, the regulatory role of Gln in a-synuclein degradation in a-synuclein-overexpressing SH-SY5Y cells was determined. The results of the present study demonstrated that Gln treatment significantly upregulated Hsp70 expression at the mRNA as well as the protein level in a dose-dependent and time-dependent manner. Gln-induced Hsp70 upregulation was found to be HSF-1-dependent, as HSF-1 knockdown abrogated the Hsp70 upregulation by Gln in a-synuclein-overexpressing SH-SY5Y cells. In conclusion, present study confirmed that Gln upregulates Hsp70 expression in SH-SY5Y neuroblastoma cells in an HSF-1-dependent manner. The upregulation of Hsp70 by Gln increases the a-synuclein degradation. Therefore, Gln may be a potential therapeutic agent to prevent a-synuclein aggregation in PD. Source
Zhu H.,Peoples Hospital of Inner Mongolia |
Yu S.-F.,Peoples Hospital of Inner Mongolia |
Bai Y.-X.,Peoples Hospital of Inner Mongolia |
Liang Y.-Y.,Peoples Hospital of Inner Mongolia |
And 2 more authors.
Experimental and Therapeutic Medicine | Year: 2015
The present study was a retrospective analysis of the dynamic changes and clinical characteristics of 231 cases of Kawasaki disease (KD) in pediatric patients admitted to the People's Hospital of Inner Mongolia between January 2003 and December 2012. A total of 37.23% of the cases occurred in the first 5 years, compared with 62.77% in the latter 5 years. The age distribution ranged from 3 months to 10 years, with a peak age of <1 year. The male-to-female ratio was 2.12:1, and the reoccurrence rate was 1.3%. Among the patient cohort, 7.8% were Mongolian children. The most common clinical symptom was fever (87.6%), while perianal skin peeling was the most rare (14.1%). With regard to the analyzed biomarkers, 90.4% of patients had abnormal platelet (PLT) counts; the next highest abnormality rates were associated with erythrocyte sedimentation rate (ESR) (74.46%) and white blood cell (WBC) counts (59.74%), followed by levels of C-reactive protein (CRP) (57.58%), creatinine kinase-MB (40.26%) and hemoglobin (Hb) (38.53%). In conclusion, the present study has found that approximately two-thirds of cases of KD over a 10-year period occurred in the latter 5 years. Changes in a number of experimental indicators, including PLT, ESR and WBC, could be used in the diagnosis of the condition and to reflect the success of the clinical treatment. © 2015, Spandidos Publications. All rights reserved. Source