Effects of Leptin on Na+/Ca2+ Exchanger in PC12 Cells

Cell Physiol Biochem. 2016;40(6):1529-1537. doi: 10.1159/000453203. Epub 2016 Dec 21.

Abstract

Background/aims: Alzheimer's disease (AD) is known to be related to alterations in neuronal intracellular calcium activity ([Ca2+]i). The present study revealed the distinct role of leptin in Na+/Ca2+-exchanger activity.

Methods: [Ca2+]i was determined utilizing Fura-2 fluorescence. The activity of NCX was measured by removal of extracellular Na+ in the presence of external Ca2+. Na+/Ca2+-exchanger activity was further quantified from whole cell currents following removal of extracellular Na+. Na+/Ca2+-exchanger isoform NCX1 transcript levels and protein abundance were quantified by RT-PCR and Western blotting, respectively.

Results: Exposure of PC12 cells to 30 µM amyloid (Aβ42) increased [Ca2+]i, an effect significantly blunted by 6 hours incubation with leptin before Aβ42 treatment. Moreover, leptin treatment significantly increased Na+/Ca2+-exchanger mediated Ca+ transport and current, NCX1 transcript level as well as NCX1 membrane protein abundance.

Conclusion: We show that leptin blunts Aβ42-evoked [Ca2+]i increase by increasing expression and activity of Na+/Ca2+-exchanger NCX1.

MeSH terms

  • Amyloid beta-Peptides / pharmacology
  • Animals
  • Calcium / metabolism
  • Cytosol / drug effects
  • Cytosol / metabolism
  • Ion Channel Gating / drug effects
  • Janus Kinase 2 / antagonists & inhibitors
  • Janus Kinase 2 / metabolism
  • Leptin / pharmacology*
  • Models, Biological
  • PC12 Cells
  • Peptide Fragments / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • Rats
  • Signal Transduction / drug effects
  • Sodium-Calcium Exchanger / genetics
  • Sodium-Calcium Exchanger / metabolism*
  • Transcription, Genetic / drug effects

Substances

  • Amyloid beta-Peptides
  • Leptin
  • Peptide Fragments
  • Protein Kinase Inhibitors
  • Sodium-Calcium Exchanger
  • amyloid beta-protein (1-42)
  • sodium-calcium exchanger 1
  • Janus Kinase 2
  • Calcium