Protective effects of atorvastatin on high glucose-induced oxidative stress and mitochondrial apoptotic signaling pathways in cultured chondrocytes.
Azam HosseinzadehKobra Bahrampour JuybariTunku KamarulAli Mohammad SharifiPublished in: Journal of physiology and biochemistry (2019)
The high glucose concentration is able to disturb chondrocyte homeostasis and contribute to OA pathogenesis. This study was designed to investigate the protective effects of atorvastatin (ATO) on high glucose (HG)-mediated oxidative stress and mitochondrial apoptosis in C28I2 human chondrocytes. The protective effect of ATO (0.01 and 0.1 μM) on HG (75 mM)-induced oxidative stress and apoptosis was evaluated in C28I2 cells. The effects of ATO on HG-induced intracellular ROS production and lipid peroxidation were detected and the protein expression levels of Bax, Bcl-2, caspase-3, total and phosphorylated JNK and P38 MAPKs were analyzed by Western blotting. The mRNA expression levels of antioxidant enzymes including heme oxygenase-1, NAD(P)H quinine oxidoreductase, glutathione S-transferase-P1, catalase, superoxide dismutase-1, glutathione peroxidase-1, -3, -4 were evaluated by reverse transcription-polymerase chain reaction. Pretreatment with ATO remarkably increased the gene expression levels of antioxidant enzymes and reduced HG-induced elevation of ROS, lipid peroxidation, Bax/Bcl-2 ratio, caspase-3 activation, and JNK and P38 phosphorylation. Atorvastatin could considerably reduce HG-induced oxidative stress and mitochondrial apoptosis through increasing the expression of antioxidant enzymes. Atorvastatin may be considered as a promising agent to prevent high glucose-induced cartilage degradation in OA patients.
Keyphrases
- high glucose
- oxidative stress
- induced apoptosis
- endothelial cells
- cell death
- dna damage
- endoplasmic reticulum stress
- diabetic rats
- cell cycle arrest
- hydrogen peroxide
- ischemia reperfusion injury
- gene expression
- signaling pathway
- fluorescent probe
- end stage renal disease
- living cells
- dna methylation
- ejection fraction
- knee osteoarthritis
- fatty acid
- poor prognosis
- prognostic factors
- heat shock
- peritoneal dialysis
- single molecule
- epithelial mesenchymal transition
- binding protein
- cell proliferation
- patient reported outcomes
- heat stress