Oxaloacetate and adipose stromal cells-conditional medium synergistically protected potassium/serum deprivation-induced neuronal apoptosis.
Adipose stromal cells conditioned media (ASC-CM) protect neurons in a variety of neuronal death models including potassium/serum deprivation-induced neuronal apoptosis. In this study, we found that ASC-CM contained glutamate oxaloacetate transaminase and its substrate, oxaloacetate (OAA) directly protected cerebellar granule neurons (CGN) from apoptosis induced by serum and potassium deprivation. Additionally, OAA inhibited serum and potassium deprivation-induced caspase 3 activation. ASC-CM and OAA in combination had a synergistic neuroprotective effect. Clearly, different from ASC-CM-induced neuroprotection, OAA-induced neuroprotection was Akt- independent but JNK-dependent. These data establish a mechanistic basis supporting that the application of ASC-CM for neuroprotective treatments could be significantly enhanced by addition of OAA.
Department of Orthopedic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, PR China.
Qingpeng
Q
Liu
School of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan, PR China; Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA.
Gang
G
Zhao
Department of Orthopedic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, PR China.
Changwei
C
Zhou
School of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan, PR China.
Martin R
MR
Farlow
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA.
Yansheng
Y
Du
Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, Jiangsu 210029, PR China. Electronic address: Guangxu_Xu@163.com.
Guangxu
G
Xu
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: huiyinggu@yahoo.com.
Huiying
H
Gu
D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D062907:Oxaloacetic Acid / Q000494:pharmacology*; D011188:Potassium / Q000032:analysis; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D018696:Neuroprotective Agents; D062907:Oxaloacetic Acid; D048670:MAP Kinase Kinase 4; C505410:Casp3 protein, rat; D053148:Caspase 3; D011188:Potassium
Adipose stromal cells; Akt; Caspase-3; JNK; Neuronal apoptosis; Neuroprotection; Oxaloacetate