title: Neuroprotective Effects of Acetyl-L-Carnitine Against Oxygen-Glucose Deprivation-Induced Neural Stem Cell Death.
abstract: Deprivation of oxygen and glucose is the main cause of neuronal cell death during cerebral infarction and can result in severe morbidity and mortality. In general, the neuroprotective therapies that are applied after ischemic stroke have been unsuccessful, despite many investigations. Acetyl-L-carnitine (ALCAR) plays an important role in mitochondrial metabolism and in modulating the coenzyme A (CoA)/acyl-CoA ratio. We investigated the protective effects of ALCAR against oxygen-glucose deprivation (OGD) in neural stem cells (NSCs). We measured cell viability, proliferation, apoptosis, and intracellular signaling protein levels after treatment with varying concentrations of ALCAR under OGD for 8 h. ALCAR protected NSCs against OGD by reducing apoptosis and restoring proliferation. Its protective effects are associated with increases in the expression of survival-related proteins, such as phosphorylated Akt (pAkt), phosphorylated glycogen synthase kinase 3b (pGSK3b), B cell lymphoma 2 (Bcl-2), and Ki-67 in NSCs that were injured by OGD. ALCAR also reduced the expression of death-related proteins, such as Bax, cytosolic cytochrome C, cleaved caspase-9, and cleaved caspase-3. We concluded that ALCAR exhibits neuroprotective effects against OGD-induced damage to NSCs by enhancing the expression of survival signals and decreasing that of death signals.
authors.affiliation: Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science & Engineering, Seoul, Republic of Korea.
authors.forename: Seong Wan
authors.initials: SW
authors.lastname: Bak
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hojin
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun-Hee
authors.initials: HH
authors.lastname: Park
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyu-Yong
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Chemistry and Research Institute of Natural Sciences, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 133-791, Republic of Korea.
authors.forename: Moon-Young
authors.initials: MY
authors.lastname: Yoon
authors.affiliation: Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science & Engineering, Seoul, Republic of Korea. ksh213@hanyang.ac.kr.|Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea. ksh213@hanyang.ac.kr.|Department of Neurology, Hanyang University College of Medicine, 249-1 Guri Hospital, Gyomun-dong, Guri-si, Gyeonggi-do, 471-701, Republic of Korea. ksh213@hanyang.ac.kr.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Koh
mesh_terms: D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000172:deficiency*; D042541:Intracellular Space / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D000108:Acetylcarnitine; D005947:Glucose; D010100:Oxygen
keywords: Acetyl-L-carnitine; Oxygen glucose deprivation; Phosphatidylinositol 3-kinase; Stroke