Acetoacetate protects neuronal cells from oxidative glutamate toxicity.
Glutamate cytotoxicity contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as epilepsy and ischemia. We previously reported that a high-fat and low-carbohydrate diet, the ketogenic diet (KD), protects against kainic acid-induced hippocampal cell death in mice. We hypothesized based on these findings that ketosis resulting from KD might inhibit glutamate cytotoxicity, resulting in inhibition of hippocampal neuronal cell death. Therefore, we investigated the role of ketone bodies [acetoacetate (AA) and beta-hydroxybutyrate (beta-OHB)] both in a mouse hippocampal cell line (HT22) and in rat primary hippocampal neurons. As a result, we found that pretreatment with 5 mM lithium AA and 4 mM Na beta-OHB protected the HT22 hippocampal cell line and primary hippocampal neuronal culture against 5 mM glutamate toxicity and that up to 2 hr of pretreatment with 5 mM AA had a protective effect against 5 mM glutamate toxicity in the HT22 cell line. Pretreatment with 5 mM AA decreased ROS production of HT22 cell line at 2 and 8 hr exposure of glutamate, and it decreased the appearance of annexin V-positive HT22 cells, which are indicative of an early stage of apoptosis, and propidium iodide-positive HT22 cells, which are indicative of necrosis.
Noh
Hae Sook
HS
Department of Anatomy and Neurobiology, Institute of Health Science, College of Medicine,Gyeongsang National University, Kyungnam, South Korea.
Hah
Young-Sool
YS
Nilufar
Rashidova
R
Han
Jaehee
J
Bong
Jae-Hwan
JH
Kang
Sang Soo
SS
Cho
Gyeong Jae
GJ
Choi
Wan Sung
WS
D000090:Acetoacetates / Q000494:pharmacology*; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007657:Ketone Bodies / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects
D000090:Acetoacetates; D017304:Annexin A5; D007657:Ketone Bodies; D017382:Reactive Oxygen Species; D017470:Receptors, Glutamate; D018698:Glutamic Acid; C016635:acetoacetic acid; D002118:Calcium