Ganoderma atrum Polysaccharide Ameliorates Hyperglycemia-Induced Endothelial Cell Death via a Mitochondria-ROS Pathway.
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.
State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China.
Wen-Juan
WJ
Li
State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China.
Shao-Ping
SP
Nie
China People's Liberation Army No. 94 Hospital, No. 1028, Jinggangshan Avenue, Nanchang 330000, China.
Yu-Fei
YF
Yao
State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China.
Xiao-Zhen
XZ
Liu
State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China.
Deng-Yin
DY
Shao
State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China.|School of Biological Sciences, The University of Auckland , Auckland, Private Bag 92019, New Zealand.
De-Ming
DM
Gong
State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China.|Guelph Food Research Center, Agriculture and Agri-Food Canada, 93 Stone Road West, Guelph, Ontario, Canada N1G 5C9.
Steve W
SW
Cui
Phillips Hydrocolloids Research Centre, Glyndwr University , Wrexham, LL11 2AW Wales, U.K.
Glyn O
GO
Phillips
State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China.|Departments of Pharmaceutical Science, Nanchang University , Nanchang 330006, China.
Ming
M
He
State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China.
Ming-Yong
MY
Xie
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D061945:Caspase Inhibitors / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects*; D032902:Ganoderma / Q000737:chemistry*; D005947:Glucose / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors; D000083162:Mitochondrial Permeability Transition Pore; D018384:Oxidative Stress / Q000187:drug effects; D011134:Polysaccharides / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014652:Vascular Diseases / Q000209:etiology / Q000517:prevention & control; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D061945:Caspase Inhibitors; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011134:Polysaccharides; D017382:Reactive Oxygen Species; D020122:tert-Butylhydroperoxide; D005947:Glucose
active Ganoderma atrum polysaccharide; apoptosis; endothelial cells; mitochondria; reactive oxygen species