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Sphingolipids increase calcium concentration in isolated rat liver nuclei
R E Catalán1, B G Miguel, M C Calcerrada
1Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de, Madrid, E-28049, Spain.
Biochemical and Biophysical Research Communications
|September 23, 1997
Summary
Sphingolipids like sphingosine and sphingosylphosphorylcholine rapidly increase nuclear calcium. This effect, partly mediated by IP3, suggests a novel sphingosine-gated calcium channel in liver nuclei.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Sphingolipids are crucial signaling molecules involved in various cellular processes.
- Nuclear calcium (Ca2+) signaling plays a vital role in regulating gene expression and cellular functions.
Purpose of the Study:
- To investigate the role of sphingolipids in modulating nuclear Ca2+ concentration.
- To elucidate the signaling pathways involved in sphingolipid-induced nuclear Ca2+ mobilization.
Main Methods:
- Measuring nuclear free Ca2+ concentration in response to sphingolipids (SPH, SPC, psychosine).
- Utilizing IP3 receptor antagonist (heparin) and phospholipase C inhibitor (U70122) to assess IP3 pathway involvement.
- Assessing the role of protein kinase C and L-type Ca2+ channels using specific inhibitors (nimodipine).
Main Results:
- Sphingosine (SPH) and sphingosylphosphorylcholine (SPC) induced a dose-dependent rise in nuclear Ca2+.
- The effect of SPH and SPC was partially mediated by inositol trisphosphate (IP3) production.
- Sphingolipid-induced Ca2+ mobilization was independent of protein kinase C but abolished by nimodipine, an L-type Ca2+ channel inhibitor.
Conclusions:
- Sphingolipids, particularly SPH and SPC, can rapidly mobilize nuclear Ca2+.
- A portion of this Ca2+ increase involves the IP3 pathway.
- The findings suggest the existence of a sphingosine-gated Ca2+-permeable channel in liver nuclei.