Leptin suppresses adenosine triphosphate-induced impairment of spinal cord astrocytes.
Spinal cord injury (SCI) causes long-term disability and has no clinically effective treatment. After SCI, adenosine triphosphate (ATP) may be released from neuronal cells and astrocytes in large amounts. Our previous studies have shown that the extracellular release of ATP increases the phosphorylation of cytosolic phospholipase A2 (cPLA2 ) and triggers the rapid release of arachidonic acid (AA) and prostaglandin E2 (PGE2) via the stimulation of epidermal growth factor receptor (EGFR) and the downstream phosphorylation of extracellular-regulated protein kinases 1 and 2. Leptin, a glycoprotein, induces the activation of the Janus kinase (JAK2)/signal transducers and activators of transcription-3 (Stat3) pathway via the leptin receptor. In this study, we found that 1) prolonged leptin treatment suppressed the ATP-stimulated release of AA and PGE2 from cultured spinal cord astrocytes; 2) leptin elevated the expression of caveolin-1 (Cav-1) via the JAK2/Stat3 signaling pathway; 3) Cav-1 blocked the interaction between Src and EGFR, thereby inhibiting the phosphorylation of EGFR and cPLA2 and attenuating the release of AA or PGE2; 4) pretreatment with leptin decreased ;he level of apoptosis and the release of interleukin-6 from cocultured neurons and astrocytes; and 5) leptin improved the recovery of locomotion in mice after SCI. Our results highlight leptin as a promising therapeutic agent for SCI. © 2016 Wiley Periodicals, Inc.
Department of Orthopaedics, First Affiliated Hospital, China Medical University, Shenyang, People's Republic of China.|Laboratory of Brain Metabolic Diseases, Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, People's Republic of China.
Baoman
B
Li
Department of Orthopaedics, First Affiliated Hospital, China Medical University, Shenyang, People's Republic of China.
Shuang
S
Qi
Department of Orthopaedics, First Affiliated Hospital, China Medical University, Shenyang, People's Republic of China.
Guangfeng
G
Sun
Department of Orthopaedics, First Affiliated Hospital, China Medical University, Shenyang, People's Republic of China.|Laboratory of Brain Metabolic Diseases, Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, People's Republic of China.
Li
L
Yang
Department of Orthopaedics, First Affiliated Hospital, China Medical University, Shenyang, People's Republic of China.
Jidong
J
Han
Department of Orthopaedics, First Affiliated Hospital, China Medical University, Shenyang, People's Republic of China.
Yue
Y
Zhu
Department of Orthopaedics, First Affiliated Hospital, China Medical University, Shenyang, People's Republic of China.|Laboratory of Brain Metabolic Diseases, Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, People's Republic of China.
Maosheng
M
Xia
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003469:Culture; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000166:cytology*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D020738:Leptin; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D054411:Receptors, Leptin; D000255:Adenosine Triphosphate; C541485:EGFR protein, mouse; D066246:ErbB Receptors
AB_10695298; AB_2072042; AB_2139987; AB_2140110; AB_2164598; AB_2224389; AB_2225021; AB_2246311; AB_2532109; AB_331796; AB_476692; AB_627288; AB_627673; AB_671714; ATP; arachidonic acid; astrocytes; caveolin-1; leptin; prostaglandin E2