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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

SPC-induced potentiation of tension development in MA. (A) Typical recordings of tension developed in rat MA to 5 min challenges with PSS containing 25 mmol/L [K+], demonstrating strong potentiation of contraction following addition of 1 µmol/L SPC compared with time control. (B) Mean data from 31 MAs (24 rats). Open symbols represent an increase in tension over control response (challenge 0 at time 0, i.e. 0 / 0) following addition of SPC. Filled symbols represent tension immediately preceding each depolarizing challenge, demonstrating a stable baseline. Bars = SEM, where not shown, smaller than symbol. ** P < 0.001 vs. control; repeated measures (RM) ANOVA on ranks, Tukey post hoc. (C) SPC-induced potentiation in MA from 24 rats at 30 min (challenge 2) in the presence of U73122 (PLC inhibitor, n = 4), Go6976 (conventional PKC inhibitor, n = 7), Go6983 (broad-spectrum PKC inhibitor, n = 6), rottlerin (putative PKCδ inhibitor, n = 5), and Y27362 (Rho kinase inhibitor, n = 7). Bars = SEM. **P < 0.001 vs. SPC alone; ††P < 0.001 vs. control; two-way ANOVA, Holm-Sidak post hoc.
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CVV029F1: SPC-induced potentiation of tension development in MA. (A) Typical recordings of tension developed in rat MA to 5 min challenges with PSS containing 25 mmol/L [K+], demonstrating strong potentiation of contraction following addition of 1 µmol/L SPC compared with time control. (B) Mean data from 31 MAs (24 rats). Open symbols represent an increase in tension over control response (challenge 0 at time 0, i.e. 0 / 0) following addition of SPC. Filled symbols represent tension immediately preceding each depolarizing challenge, demonstrating a stable baseline. Bars = SEM, where not shown, smaller than symbol. ** P < 0.001 vs. control; repeated measures (RM) ANOVA on ranks, Tukey post hoc. (C) SPC-induced potentiation in MA from 24 rats at 30 min (challenge 2) in the presence of U73122 (PLC inhibitor, n = 4), Go6976 (conventional PKC inhibitor, n = 7), Go6983 (broad-spectrum PKC inhibitor, n = 6), rottlerin (putative PKCδ inhibitor, n = 5), and Y27362 (Rho kinase inhibitor, n = 7). Bars = SEM. **P < 0.001 vs. SPC alone; ††P < 0.001 vs. control; two-way ANOVA, Holm-Sidak post hoc.

Mentions: As previously reported for rat IPA,10 1 µmol/L SPC alone had no effect on tension in rat or mouse MA (e.g. Figures 1A and 2A), or rat renal or femoral artery.Figure 1


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)

SPC-induced potentiation of tension development in MA. (A) Typical recordings of tension developed in rat MA to 5 min challenges with PSS containing 25 mmol/L [K+], demonstrating strong potentiation of contraction following addition of 1 µmol/L SPC compared with time control. (B) Mean data from 31 MAs (24 rats). Open symbols represent an increase in tension over control response (challenge 0 at time 0, i.e. 0 / 0) following addition of SPC. Filled symbols represent tension immediately preceding each depolarizing challenge, demonstrating a stable baseline. Bars = SEM, where not shown, smaller than symbol. ** P < 0.001 vs. control; repeated measures (RM) ANOVA on ranks, Tukey post hoc. (C) SPC-induced potentiation in MA from 24 rats at 30 min (challenge 2) in the presence of U73122 (PLC inhibitor, n = 4), Go6976 (conventional PKC inhibitor, n = 7), Go6983 (broad-spectrum PKC inhibitor, n = 6), rottlerin (putative PKCδ inhibitor, n = 5), and Y27362 (Rho kinase inhibitor, n = 7). Bars = SEM. **P < 0.001 vs. SPC alone; ††P < 0.001 vs. control; two-way ANOVA, Holm-Sidak post hoc.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4362402&req=5

CVV029F1: SPC-induced potentiation of tension development in MA. (A) Typical recordings of tension developed in rat MA to 5 min challenges with PSS containing 25 mmol/L [K+], demonstrating strong potentiation of contraction following addition of 1 µmol/L SPC compared with time control. (B) Mean data from 31 MAs (24 rats). Open symbols represent an increase in tension over control response (challenge 0 at time 0, i.e. 0 / 0) following addition of SPC. Filled symbols represent tension immediately preceding each depolarizing challenge, demonstrating a stable baseline. Bars = SEM, where not shown, smaller than symbol. ** P < 0.001 vs. control; repeated measures (RM) ANOVA on ranks, Tukey post hoc. (C) SPC-induced potentiation in MA from 24 rats at 30 min (challenge 2) in the presence of U73122 (PLC inhibitor, n = 4), Go6976 (conventional PKC inhibitor, n = 7), Go6983 (broad-spectrum PKC inhibitor, n = 6), rottlerin (putative PKCδ inhibitor, n = 5), and Y27362 (Rho kinase inhibitor, n = 7). Bars = SEM. **P < 0.001 vs. SPC alone; ††P < 0.001 vs. control; two-way ANOVA, Holm-Sidak post hoc.
Mentions: As previously reported for rat IPA,10 1 µmol/L SPC alone had no effect on tension in rat or mouse MA (e.g. Figures 1A and 2A), or rat renal or femoral artery.Figure 1

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