2-Deoxy-d-glucose protects neural progenitor cells against oxidative stress through the activation of AMP-activated protein kinase.
2-Deoxy-d-glucose (2DG) is an analog of glucose that is effectively taken up by cells competing with normal glucose but cannot be further utilized to produce energy. It was previously reported that 2DG can mimic the beneficial effects of dietary restriction in experimental models of neurodegenerative disorders and cancer. In the present study, we report that pretreatment with 2DG increases the resistance of neural progenitor cells (NPC) to oxidative insults. 2DG significantly suppressed the proliferation of NPC, and high concentrations of 2DG were toxic to NPC. However, a treatment with a moderate concentration of 2DG protected the NPC against tBHP-induced oxidative stress suggesting that this chemical had hormetic action mimicking dietary restriction. Furthermore, we showed that the protective mechanism of 2DG involved the activation of AMP-activated protein kinase. Our findings demonstrate that 2DG can modulate the cellular responses to oxidative stress and confer cellular resistance in NPC by activating the metabolic regulator.
Park
Mikyung
M
Department of Pharmacy, Pusan National University, Geumjeong-gu, Busan 609-735, Republic of Korea.
Song
Kwan Sung
KS
Kim
Hyun Kyu
HK
Park
Young Joo
YJ
Kim
Hyung Sik
HS
Bae
Min In
MI
Lee
Jaewon
J
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects*; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D020122:tert-Butylhydroperoxide / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D012265:Ribonucleotides; D013778:Tetrazolium Salts; D013844:Thiazoles; D000620:Aminoimidazole Carboxamide; D020122:tert-Butylhydroperoxide; D003847:Deoxyglucose; D007770:L-Lactate Dehydrogenase; D055372:AMP-Activated Protein Kinases; C022616:thiazolyl blue; C031143:AICA ribonucleotide