Ganoderma atrum Polysaccharide Ameliorates Hyperglycemia-Induced Endothelial Cell Death via a Mitochondria-ROS Pathway

Abstract

The aim of the present study was to examine the role of Ganoderma atrum polysaccharide (PSG-1) in reactive oxygen species (ROS) generation and mitochondrial function in hyperglycemia-induced angiopathy. In this work, ROS scavenger, oxidizing agent tert-butylhydroperoxide (tBH), mitochondrial permeability transition pore (mPTP) blockers, and caspase inhibition are used to investigate whether PSG-1 may promote survival of human umbilical vein cells (HUVECs) through preventing the overproduction of ROS and mitochondrial dysfunction. Experimental results show that exposure of HUVECs to 35.5 mmol/L glucose increases the proportion of cells undergoing apoptosis. PSG-1, mPTP blocker, or caspase inhibition can reduce apoptosis and ROS generation. PSG-1 also increases mitochondrial Bcl-2 protein formation and mitochondrial membrane potential (ΔΨm) but inhibits Bax translocation, cytochrome c release, and caspase activation. In summary, vascular protection of PSG-1 can be mediated by a mitochondria-ROS pathway. ROS generation and mPTP induction are critical for high glucose-mediated apoptosis. PSG-1 ameliorates endothelial dysfunction by inhibiting oxidative stress and subsequent mitochondrial dysfunction.

A mix of apple pomace polysaccharide improves mitochondrial function and reduces oxidative stress in the liver of high‐fat diet‐induced obese mice

“…The mitochondria are a major source of ROS, which is particularly susceptible to oxidative stress . Previous studies have shown that Astragalus and Cornus polysacharides inhibits mitochondrial injury caused by the continuous production of free radicals and selective oxidative damage , and Ganoderma atrum polysacharides protect mitochondrial by scavenging ROS , increasing the activity of antioxidant enzymes, and Astragalus and ginseng polysacharides ameliorating mitochondrial dysfunction, which ultimately improved energy metabolism . In the present study, we found that palmitate‐treated HepG2 cells showed marked changes in several parameters of the mitochondrial function (Fig.…”

“…There are mounting evidences that HFD‐induced oxidative stress resulting from the overproduction of ROS is a major factor contributing to the development and progression of liver damage. The collapse of the MMP results in the rapid release of cytochrome C into the cytoplasm . In the present study, palmitate‐treated HepG2 cells showed a marked increased generation of mitochondrial ROS (Fig.…”

Effect of Content of Sulfate Groups in Seaweed Polysaccharides on Antioxidant Activity and Repair Effect of Subcellular Organelles in Injured HK‐2 Cells

“…Cui et al [38] studied the protective effect of sulfated polysaccharide (such as SJP) against 6-OHDA-induced SH-SY5Y cell death and found that the Δ Ψ m of SJP pretreatment group (79%) was higher than 6-OHDA damaged group (56%), suggesting that SJP had certain protective effect on 6-OHDA-induced SH-SY5Y cell damage. Li et al [39] examined the endothelial cell death mode caused by high glucose-induced ROS and suggested that Ganoderma atrum polysaccharide (PSG-1) had protective effect on the Δ Ψ m. The Δ Ψ m (36.26%) of high glucose-treated group was obviously lower than the cell of the control group (80.44%), but the Δ Ψ m increased (60.03%) after the cells were pretreated by PSG-1.…”

“…Li et al [39] examined the high glucose-induced ROS production and cell apoptosis of endothelial cells and suggested that the cell apoptotic rate of high glucose treatment group was 20.66%, whereas the cell apoptotic rate reduced to 12.68% after the cells were pretreated with PSG-1, which indicated that PSG-1 can alleviate cell apoptosis induced by oxidative stress. Similarly, Chowdhury et al [49] revealed that the bacterial fucoidan can inhibit the H 2 O 2 -induced stress of human lung fibroblasts, and the total cell apoptotic rate of H 2 O 2 -damaged group and polysaccharide repair group was 42.6% and 10.0%, respectively.…”

Design of a phosphinate‐based bioluminescent probe for superoxide radical anion imaging in living cells

“…ROS include superoxide anion (O 2 ˙ − ), peroxynitrite (ONOO − ), nitric oxide (NO), hydrogen peroxide (H 2 O 2 ) and hydroxyl radical (·OH) . Although normal ROS regulation is crucial for cellular functions , aberrant production of ROS is related to many diseases , such as Alzheimer's disease , Parkinson's disease , diabetes , cancer , etc. Note that O 2 ˙ − is one of the major ROS due to its highly oxidative activity.…”