Abstract
(1) Aims: The present study aimed to observe the effects of Ginsenoside Rb1 on high glucose-induced endothelial damage in rat retinal capillary endothelial cells (RCECs) and to investigate the underlying mechanism. (2) Methods: Cultured RCECs were treated with normal glucose (5.5 mM), high glucose (30 mM glucose), or high glucose plus Rb1 (20 μM). Cell viability, lactate dehydrogenase (LDH) levels, the mitochondrial DNA copy number, and the intracellular ROS content were measured to evaluate the cytotoxicity. Superoxide dismutase (SOD), catalase (CAT), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), poly(ADP-ribose) polymerase (PARP), and sirtuin (SIRT) activity was studied in cell extracts. Nicotinamide adenine dinucleotide (NAD+)/NADH, NADPH/NADP+, and glutathione (GSH)/GSSG levels were measured to evaluate the redox state. The expression of nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), SIRT1, and SIRT3 was also evaluated after Rb1 treatment. (3) Results: Treatment with Rb1 significantly increased the cell viability and mtDNA copy number, and inhibited ROS generation. Rb1 treatment increased the activity of SOD and CAT and reduced the activity of NOX and PARP. Moreover, Rb1 enhanced both SIRT activity and SIRT1/SIRT3 expression. Additionally, Rb1 was able to re-establish the cellular redox balance in RCECs. However, Rb1 showed no effect on NMNAT1 expression in RCECs exposed to high glucose. (4) Conclusion: Under high glucose conditions, decreases in the reducing power may be linked to DNA oxidative damage and apoptosis via activation of the NMNAT-NAD-PARP-SIRT axis. Rb1 provides an advantage during high glucose-induced cell damage by targeting the NAD-PARP-SIRT signaling pathway and modulating the redox state in RCECs.
Highlights
Diabetic retinopathy (DR) is one of the major complications of diabetes mellitus (DM) and is the leading cause of vision loss and blindness among working-age people in developed countries [1]
Several investigators have shown that the hyperglycemic environment present in DM leads to enhanced reactive oxygen species (ROS) production, DNA damage, and a decrease in nicotinamide adenine dinucleotide (NAD+) levels, all of which have been linked to a decrease in sirtuins (SIRT) expression and involve the activation of poly(ADP-ribose) polymerase (PARP) [10,11,12]
The retinal capillary endothelial cells (RCECs) were analyzed for the expression and localization of endothelial cell markers by the immunofluorescence staining of CD31 and the von Willebrand factor
Summary
Diabetic retinopathy (DR) is one of the major complications of diabetes mellitus (DM) and is the leading cause of vision loss and blindness among working-age people in developed countries [1]. Previous studies have found that retinal endothelial cell apoptosis is an early event in DR. Exposure of the retinal vasculature to high glucose results in a loss of retinal capillary endothelial cells (RCECs) through apoptosis [2]. Additional studies using human RCECs [3], bovine RCECs [4], and rat RCECs [5] have reported an increase in apoptosis when cells are exposed to high glucose. Whether high glucose can induce NMNAT1 expression in RCECs remains unknown
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