The protective role of 5-HMF against hypoxic injury.
In an attempt to find new types of anti-hypoxic agents from herbs, we identified 5-hydroxymethyl-2-furfural (5-HMF) as a natural agent that fulfills the criterion. 5-HMF, the final product of carbohydrate metabolism, has favorable biological effects such as anti-oxidant activity and inhibiting sickling of red blood cells. The role of 5-HMF in hypoxia, however, is not yet. Our pilot results showed that pretreatment with 5-HMF markedly increased both the survival time and the survival rate of mice under hypoxic stress. The present study was aimed to further investigate the protective role of 5-HMF and the underlying mechanisms in hypoxic injury using ECV304 cells as an in vitro model. ECV304 cells pretreated with or without 5-HMF for 1 h were exposed to hypoxic condition (0.3% O(2)) for 24 h and then cell apoptosis, necrosis, the changes of mitochondrial membrane potential (MMP) and the expressions of phosphorylation- extracellular signal-regulated kinase (p-ERK) were investigated. Pretreatment with 5-HMF markedly attenuated hypoxia-induced cell necrosis and apoptosis at late stage (p < 0.01). Furthermore, pretreatment with 5-HMF rescued both the decline of the MMP and the increase of p-ERK protein under hypoxia. In a word, these results indicated that 5-HMF had protective effects against hypoxic injury in ECV304 cells, and its effects on MMP and p-ERK may be involved in the mechanism.
Beijing Institute for Neuro-Science, Capital Medical University School of Basic Medical Sciences, No. 27 Taiping Road, Beijing, People's Republic of China.
Ming-Ming
MM
Li
Li-Ying
LY
Wu
Tong
T
Zhao
Lei
L
Xiong
Xin
X
Huang
Zhao-Hui
ZH
Liu
Xue-Lai
XL
Fan
Cheng-Rong
CR
Xiao
Yue
Y
Gao
Yun-Bao
YB
Ma
Ji-Jun
JJ
Chen
Ling-Ling
LL
Zhu
Ming
M
Fan
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009336:Necrosis; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D020011:Protective Agents; C008046:5-hydroxymethylfurfural; D005662:Furaldehyde; D007770:L-Lactate Dehydrogenase; D048049:Extracellular Signal-Regulated MAP Kinases