High glucose-induced oxidative stress promotes autophagy through mitochondrial damage in rat notochordal cells

Abstract

Purpose Diabetes mellitus is associated with an increased risk of intervertebral disc degeneration (IDD). Reactive oxygen species (ROS), oxidative stressors, play a key role in autophagy of diabetes-associated diseases. Mitochondria are known to be the main source of endogenous ROS in most mammalian cell types. The authors therefore conducted the following study to evaluate the effects of high glucose concentrations on the induction of oxidative stress and autophagy through mitochondrial damage in rat notochordal cells. Methods Rat notochordal cells were isolated, cultured, and placed in either 10 % fetal bovine serum (normal control) or 10 % fetal bovine serum plus two different high glucose concentrations (0.1 M and 0.2 M) (experimental conditions) for one and three days, respectively. We identified and quantified the mitochondrial damage (mitochondrial transmembrane potential) and the generation of ROS and antioxidants (manganese superoxide dismutase [MnSOD] and catalase). We also investigated expressions and activities of autophagy markers (beclin-1, light chain3-I [LC3-I] and LC3-II, autophagy-related gene [Atg] 3,5,7,and 12). Results An enhanced disruption of mitochondrial transmembrane potential, which indicates mitochondrial damage, was identified in rat notochordal cells treated with both high glucose concentrations. Both high glucose concentrations increased production of ROS by rat notochordal cells in a dose-and time-dependent manner. The two high glucose solutions also enhanced rat notochordal cells' compensatory expressions of MnSOD and catalase in a dose-and timedependent manner. The proautophagic effects of high glucose concentrations were manifested in the form of enhanced rat notochordal cells' expressions of beclin-1, LC3-II, Atg3, 5, 7, and 12 in a dose-and time-dependent manner. The ratio of LC3-II/LC3-I expression was also increased in a dose-and time-dependent manner. Conclusions The findings from this study demonstrate that high glucose-induced oxidative stress promotes autophagy through mitochondrial damage of rat notochordal cells in a dose-and time-dependent manner. These results suggest that preventing the generation of oxidative stress might be a novel therapeutic target by which to prevent or to delay IDD in patients with diabetes mellitus.

Accelerated premature stress-induced senescence of young annulus fibrosus cells of rats by high glucose-induced oxidative stress

“…Untreated DM can cause many complications, such as cardiovascular disease, chronic renal failure, retinopathy and neuropathy [2]. DM is also considered to be an important aetiological factor in intervertebral disc degeneration [3][4][5]. Previous studies have reported a higher incidence of degenerative disc diseases in patients with DM than in the patients without DM [6].…”

Comment on Park et al.: High glucose-induced oxidative stress promotes autophagy through mitochondrial damage in rat notochordal cells

“…Dear Editor, Recently, we read with great interest the article by Park et al [1], who demonstrated that high glucose could impair the transmembrane potential, increase production of reactive oxygen species and activate autophagy in rat notochordal cells. The result of this research is consistent with our previous study, which indicated that autophagy was increased in rats with type I diabetes mellitus [2].…”

Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis

“…24 Autophagy can also be induced by high glucose levels in various cell types, partly through hyperglycemia-mediated reactive oxygen species production, and has protective effects in vitro. [47][48][49] In fact, activation of MTOR was associated with an accelerated glomerular injury of DN-or puromycin models potentially suggesting an involvement of autophagy in these disease models 50,51 Nevertheless, the direct role of autophagy in diabetic nephropathy is not fully understood. Thus, the objective of this study was to investigate the precise involvement of podocyte and endothelial autophagy in the pathogenesis of diabetic nephropathy in vivo.…”