ABSTRACT
For a long time, hydrogen (H) has been considered as a physiological inert gas. However, recent studies have demonstrated that molecular H exerts significant therapeutic effects on various disease models due to its antioxidative, anti-inflammatory and anti-apoptotic capabilities, which have also been well confirmed in many clinical trials. Cardiovascular and cerebrovascular diseases (CCVDs) are the leading cause of death in the world, constituting a serious threat to human life and public health. In this paper, we reviewed the latest research progress of the biomedical effects of H in CCVDs and its possible molecular mechanisms, in the hope of providing new clues for the treatment of some CCVDs.
ABSTRACT
High-density lipoprotein (HDL) is composed of apolipoproteins, lipids and functional proteins. HDL protects against atherosclerosis (AS) by reverse cholesterol transport (RCT). HDL inhibits the lipid oxidation, inflammation and restores endothelial function. During systemic inflammation or metabolic disorders, HDL can be modified abnormally and converted to a dysfunctional type, which results in the loss of anti-inflammatory factors including apolipoprotein A-I (apoA-I), paraoxonase (PON) and platelet activating factor acetylhydrolase (PAF-AH), and gains of pro-inflammatory factors such as serum amyloid A (SAA), triglyceride (TG) and oxidative lipid. Therefore, understanding the changes in compositions and biological functions of dysfunctional HDL might help to comprehend its pathogenic mechanism.
ABSTRACT
Pigment epithelium-derived factor (PEDF) is a multifunctional protein with anti-inflammatory, antioxidant and antithrombotic properties and plays a protective role against atherosclerosis (AS). The purpose of the present study is to explore the effects of oxidized low density lipoprotein (ox-LDL) on the expression of PEDF in cultured human umbilical vein endothelial cells (HUVECs). HUVECs were cultured and incubated with ox-LDL at different concentrations (6.25, 12.5, 25, 50, 100 and 150 mg/L) for 24 h. Apoptosis of endothelial cells were assayed by morphological staining and flow cytometry. The intracellular reactive oxygen species (ROS) levels were measured by flow cytometry. Cell viability was assayed by MTT assay. PEDF protein and mRNA expressions in HUVECs were analyzed by Western blot and quantitative real-time PCR, respectively. The results showed that ox-LDL significantly induced apoptosis, reduced cell viability, increased intracellular ROS levels and decreased the PEDF expression in HUVECs in a concentration-dependent manner. Ox-LDL at 50 mg/L obviously decreased the PEDF protein expression compared with control group (P < 0.05), whereas 25 mg/L ox-LDL already markedly reduced the PEDF mRNA expression (P < 0.05). In conclusion, the results suggest that ox-LDL down-regulates the PEDF expression through an increased ox-LDL-induced intracellular production of ROS.
Subject(s)
Humans , Apoptosis , Cells, Cultured , Down-Regulation , Eye Proteins , Metabolism , Human Umbilical Vein Endothelial Cells , Cell Biology , Lipoproteins, LDL , Pharmacology , Nerve Growth Factors , Metabolism , Reactive Oxygen Species , Metabolism , Serpins , MetabolismABSTRACT
The present study was to investigate the effects of exogenous insulin-like growth factor binding protein 7 (IGFBP7) on the proliferation of human breast cancer cell line MDA-MB-453 and its possible mechanism. By means of MTT method in vitro, the results showed exogenous IGFBP7 inhibited the growth of MDA-MB-453 cells (IC50 of IGFBP7 = 8.49 μg/mL) in time- and concentration-dependent manner. SB203580, p38(MAPK) inhibitor, blocked the anti-proliferative effect of exogenous IGFBP7. The flow cytometry assay showed that exogenous IGFBP7 remarkably induced G0/G1 arrest in MDA-MB-453 cells. The Western blot showed that exogenous IGFBP7 promoted phosphorylation of p38(MAPK), up-regulated expression of p21(CIP1/WAF1), and inhibited phosphorylation of Rb. SB203580 restrained exogenous IGFBP7-induced regulation of p21(CIP1/WAF1) and p-Rb in MDA-MB-453 cells. In conclusion, the present study suggests that exogenous IGFBP7 could activate the p38(MAPK) signaling pathway, upregulate p21(CIP1/WAF1) expression, inhibit phosphorylation of Rb, and finally induce G0/G1 arrest in MDA-MB-453 cells.
Subject(s)
Female , Humans , Breast Neoplasms , Pathology , Cell Line, Tumor , Cell Proliferation , Cyclin-Dependent Kinase Inhibitor p21 , Metabolism , Imidazoles , Pharmacology , Insulin-Like Growth Factor Binding Proteins , Pharmacology , Phosphorylation , Pyridines , Pharmacology , Signal Transduction , Somatomedins , p38 Mitogen-Activated Protein Kinases , MetabolismABSTRACT
The purpose of the present study is to explore the effect of oxidized low density lipoprotein (ox-LDL) on the induction of endoplasmic reticulum stress (ERS) and the underlying mechanisms in ox-LDL-induced macrophage foam-forming process. RAW264.7 macrophages were cultured in DMEM medium containing 10% fetal bovine serum, and then treated with ox-LDL (25, 50 and 100 mg/L), anti-CD36 monoclonal antibody+ox-LDL and tunicamycin (TM), respectively. After incubation for 24 h, the cells were collected. The cellular lipid accumulation was showed by oil red O staining and the content of cellular total cholesterol was quantified by enzymatic colorimetry. The expression of glucose-regulated protein 94 (GRP94), a molecular marker of ERS, was determined by immunocytochemistry assay. The levels of GRP94 protein, phosphorylated inositol-requiring enzyme 1 (p-IRE1) and X box binding protein 1 (XBP1) in RAW264.7 cells were detected by Western blotting. The results indicated that after incubation with ox-LDL (25, 50 and 100 mg/L) for 24 h, a large amount of lipid droplets were found in the cytoplasm, and the contents of cellular total cholesterol were increased by 2.1, 2.8 and 3.1 folds compared with the control, respectively. Anti-CD36 antibody decreased markedly the cellular lipid accumulation induced by ox-LDL at 100 mg/L. Both ox-LDL and TM, a specific ERS inducer, could up-regulate the protein expression of GRP94 in a dose-dependent manner. Furthermore, p-IRE1 and XBP1, two key components of the unfolded protein response, were also significantly induced by the treatment with ox-LDL. The up-regulations of the three proteins induced by ox-LDL were inhibited significantly when the macrophages were pre-incubated with anti-CD36 antibody. These results suggest that ox-LDL may induce ERS in a dose-dependent way and subsequently activate the unfolded protein response signaling pathway in RAW264.7 macrophages, which is potentially mediated by scavenger receptor CD36.