Identification and characterization of a leptin-responsive neuroblastoma cell line.
The adipocyte-derived hormone leptin plays a critical role in a variety of physiological and pathological actions. As such the determination of leptin signal transduction pathways are important both for understanding the molecular mechanisms of leptin action and for identifying sites for possible therapeutic intervention. Since the hypothalamus is the primary site of leptin action, we sought to identify a neuronal-derived human cell line containing the long form of the leptin receptor (OBRb). To this end, we screened several neuroblastoma cell lines and isolated a sub-line of SH-SY5Y cells, which we designated as SH-OBRb, for further studies. We characterized the transduction pathways induced by leptin in SH-OBRb cells and demonstrated that OBRb mediates tyrosine phosphorylation of STAT3, phosphorylation of ERK1/2, but not SAPK/JNK and p38 MAPK, in a dose and time dependent fashion. In addition, Akt appears to be phosphorylated in the basal state and to be insensitive to further activation by leptin. In summary, we have isolated a unique cell line that can be utilized as a model for use in the study of leptin action and molecular mechanisms.
Wang
Ruduan
R
Department of Cardiovascular, Metabolic and Endocrine Diseases, Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA.
Swick
Andrew G
AG
D045744:Cell Line, Tumor; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014443:Tyrosine / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D020738:Leptin; D050796:STAT3 Transcription Factor; D014443:Tyrosine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4