Limits...
Sphingosylphosphorylcholine potentiates vasoreactivity and voltage-gated Ca2+ entry via NOX1 and reactive oxygen species.

Shaifta Y, Snetkov VA, Prieto-Lloret J, Knock GA, Smirnov SV, Aaronson PI, Ward JP - Cardiovasc. Res. (2015)

Bottom Line: The intracellular superoxide generator LY83583 mimicked the effect of SPC.In patch-clamped mesenteric artery cells, SPC (200 nmol/L) enhanced Ba2+ current through L-type Ca2+ channels, an action abolished by Tempol but mimicked by LY83583.Our results suggest that low concentrations of SPC activate a PLC-coupled and NOX1-mediated increase in ROS, with consequent enhancement of voltage-gated Ca2+ entry and thus vasoreactivity.

View Article: PubMed Central - PubMed

Affiliation: Division of Asthma, Allergy, and Lung Biology, King's College London, 5th Floor Tower Wing, Guy's Campus, London SE1 9RT, UK.

No MeSH data available.


Related in: MedlinePlus

Effects of inhibitors on SPC-induced potentiation in MA and IPA. (A) SPC-induced potentiation (challenge 2) of MA for SPC alone (n = 31, 24 rats), and in the presence of PKCε peptide inhibitor (n = 6), PP2 (Src inhibitor, n = 7), Tempol (n = 11, 8 rats), and VAS2870 (NOX inhibitor, n = 4); 24 rats. (B) SPC-induced potentiation (challenge 2) of IPA for SPC alone (n = 47, 30 rats), and in the presence of PKCε peptide inhibitor (n = 8), PP2 (n = 8), Tempol (n = 11), and VAS2870 (n = 4); 20 rats. (C) Typical trace showing reversal of SPC-induced potentiation in a MA by addition of Tempol (3 mmol/L). Bars = SEM. **P < 0.001 vs. SPC alone; two-way ANOVA, Holm-Sidak post hoc.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4362402&req=5

CVV029F3: Effects of inhibitors on SPC-induced potentiation in MA and IPA. (A) SPC-induced potentiation (challenge 2) of MA for SPC alone (n = 31, 24 rats), and in the presence of PKCε peptide inhibitor (n = 6), PP2 (Src inhibitor, n = 7), Tempol (n = 11, 8 rats), and VAS2870 (NOX inhibitor, n = 4); 24 rats. (B) SPC-induced potentiation (challenge 2) of IPA for SPC alone (n = 47, 30 rats), and in the presence of PKCε peptide inhibitor (n = 8), PP2 (n = 8), Tempol (n = 11), and VAS2870 (n = 4); 20 rats. (C) Typical trace showing reversal of SPC-induced potentiation in a MA by addition of Tempol (3 mmol/L). Bars = SEM. **P < 0.001 vs. SPC alone; two-way ANOVA, Holm-Sidak post hoc.

Mentions: The above precludes any role for PKCδ, suggesting involvement of PKCε, another novel isoform which has been implicated in the actions of SPC.28 We were unable to source PKCε−/− mice, but utilized instead the specific PKCε translocation inhibitor peptide (Glu-Ala-Val-Ser-Leu-Lys-Pro-Thr).29 This strongly suppressed SPC-induced potentiation of depolarization-induced contraction in both MA and IPA (Figure 3A and B). SPC (1 µmol/L) also caused translocation of PKCε in cultured PASMCs and MASMCs (see Supplementary material online, Figure S1).Figure 3


Sphingosylphosphorylcholine potentiates vasoreactivity and voltage-gated Ca2+ entry via NOX1 and reactive oxygen species.

Shaifta Y, Snetkov VA, Prieto-Lloret J, Knock GA, Smirnov SV, Aaronson PI, Ward JP - Cardiovasc. Res. (2015)

Effects of inhibitors on SPC-induced potentiation in MA and IPA. (A) SPC-induced potentiation (challenge 2) of MA for SPC alone (n = 31, 24 rats), and in the presence of PKCε peptide inhibitor (n = 6), PP2 (Src inhibitor, n = 7), Tempol (n = 11, 8 rats), and VAS2870 (NOX inhibitor, n = 4); 24 rats. (B) SPC-induced potentiation (challenge 2) of IPA for SPC alone (n = 47, 30 rats), and in the presence of PKCε peptide inhibitor (n = 8), PP2 (n = 8), Tempol (n = 11), and VAS2870 (n = 4); 20 rats. (C) Typical trace showing reversal of SPC-induced potentiation in a MA by addition of Tempol (3 mmol/L). Bars = SEM. **P < 0.001 vs. SPC alone; two-way ANOVA, Holm-Sidak post hoc.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4362402&req=5

CVV029F3: Effects of inhibitors on SPC-induced potentiation in MA and IPA. (A) SPC-induced potentiation (challenge 2) of MA for SPC alone (n = 31, 24 rats), and in the presence of PKCε peptide inhibitor (n = 6), PP2 (Src inhibitor, n = 7), Tempol (n = 11, 8 rats), and VAS2870 (NOX inhibitor, n = 4); 24 rats. (B) SPC-induced potentiation (challenge 2) of IPA for SPC alone (n = 47, 30 rats), and in the presence of PKCε peptide inhibitor (n = 8), PP2 (n = 8), Tempol (n = 11), and VAS2870 (n = 4); 20 rats. (C) Typical trace showing reversal of SPC-induced potentiation in a MA by addition of Tempol (3 mmol/L). Bars = SEM. **P < 0.001 vs. SPC alone; two-way ANOVA, Holm-Sidak post hoc.
Mentions: The above precludes any role for PKCδ, suggesting involvement of PKCε, another novel isoform which has been implicated in the actions of SPC.28 We were unable to source PKCε−/− mice, but utilized instead the specific PKCε translocation inhibitor peptide (Glu-Ala-Val-Ser-Leu-Lys-Pro-Thr).29 This strongly suppressed SPC-induced potentiation of depolarization-induced contraction in both MA and IPA (Figure 3A and B). SPC (1 µmol/L) also caused translocation of PKCε in cultured PASMCs and MASMCs (see Supplementary material online, Figure S1).Figure 3

Bottom Line: The intracellular superoxide generator LY83583 mimicked the effect of SPC.In patch-clamped mesenteric artery cells, SPC (200 nmol/L) enhanced Ba2+ current through L-type Ca2+ channels, an action abolished by Tempol but mimicked by LY83583.Our results suggest that low concentrations of SPC activate a PLC-coupled and NOX1-mediated increase in ROS, with consequent enhancement of voltage-gated Ca2+ entry and thus vasoreactivity.

View Article: PubMed Central - PubMed

Affiliation: Division of Asthma, Allergy, and Lung Biology, King's College London, 5th Floor Tower Wing, Guy's Campus, London SE1 9RT, UK.

No MeSH data available.


Related in: MedlinePlus