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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: At lower concentrations (≤1 µmol/L), however, it does not constrict intrapulmonary arteries (IPAs), but strongly potentiates vasoreactivity.The intracellular superoxide generator LY83583 mimicked the effect of SPC.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

The ROS generator LY83583 mimics the effect of SPC. (A) Typical tension recordings from rat MA and IPA for 5 min challenges with PSS containing ∼25 mmol/L [K+] and following addition of 1 µmol/L LY83583, showing potentiation of the response. (B) LY83583 (LY)-induced potentiation at 30 min in 9 MA (5 rats) and 9 IPA (5 rats), and in the presence of Go6983 (Go, 4 MA and 4 IPA), PP2 (11 MA and 8 IPA), and VAS2870 (VAS, 6 MA); 18 rats. Bars = SEM. ††P < 0.001 vs. control (no LY83583); no inhibitor had any significant effect; one-way ANOVA, Holm-Sidak post hoc.
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CVV029F6: The ROS generator LY83583 mimics the effect of SPC. (A) Typical tension recordings from rat MA and IPA for 5 min challenges with PSS containing ∼25 mmol/L [K+] and following addition of 1 µmol/L LY83583, showing potentiation of the response. (B) LY83583 (LY)-induced potentiation at 30 min in 9 MA (5 rats) and 9 IPA (5 rats), and in the presence of Go6983 (Go, 4 MA and 4 IPA), PP2 (11 MA and 8 IPA), and VAS2870 (VAS, 6 MA); 18 rats. Bars = SEM. ††P < 0.001 vs. control (no LY83583); no inhibitor had any significant effect; one-way ANOVA, Holm-Sidak post hoc.

Mentions: The above results suggest that SPC-induced potentiation of vasoreactivity is mediated via a PLC-, PKCε- and Src-dependent activation of NOX1, and consequent generation of ROS. We therefore examined whether exogenous ROS could mimic the effects of SPC using LY83583, a membrane-permeable quinolinequinone that acts within the cell to generate intracellular superoxide.20,36 At 1 µmol/L, LY83583 does not itself alter vascular tension20,36 (and see Figure 6A), but like SPC it substantially enhanced the response to depolarization with ∼25 mmol/L [K+] in both MA and IPA (Figure 6A and B; P < 0.001). In contrast to SPC, however, the effects were not significantly inhibited by Gö6983, PP2, or VAS2870 (Figure 6B), consistent with ROS being downstream of PKCε- and Src-mediated activation of NOX1.Figure 6


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)

The ROS generator LY83583 mimics the effect of SPC. (A) Typical tension recordings from rat MA and IPA for 5 min challenges with PSS containing ∼25 mmol/L [K+] and following addition of 1 µmol/L LY83583, showing potentiation of the response. (B) LY83583 (LY)-induced potentiation at 30 min in 9 MA (5 rats) and 9 IPA (5 rats), and in the presence of Go6983 (Go, 4 MA and 4 IPA), PP2 (11 MA and 8 IPA), and VAS2870 (VAS, 6 MA); 18 rats. Bars = SEM. ††P < 0.001 vs. control (no LY83583); no inhibitor had any significant effect; one-way ANOVA, Holm-Sidak post hoc.
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Related In: Results  -  Collection

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CVV029F6: The ROS generator LY83583 mimics the effect of SPC. (A) Typical tension recordings from rat MA and IPA for 5 min challenges with PSS containing ∼25 mmol/L [K+] and following addition of 1 µmol/L LY83583, showing potentiation of the response. (B) LY83583 (LY)-induced potentiation at 30 min in 9 MA (5 rats) and 9 IPA (5 rats), and in the presence of Go6983 (Go, 4 MA and 4 IPA), PP2 (11 MA and 8 IPA), and VAS2870 (VAS, 6 MA); 18 rats. Bars = SEM. ††P < 0.001 vs. control (no LY83583); no inhibitor had any significant effect; one-way ANOVA, Holm-Sidak post hoc.
Mentions: The above results suggest that SPC-induced potentiation of vasoreactivity is mediated via a PLC-, PKCε- and Src-dependent activation of NOX1, and consequent generation of ROS. We therefore examined whether exogenous ROS could mimic the effects of SPC using LY83583, a membrane-permeable quinolinequinone that acts within the cell to generate intracellular superoxide.20,36 At 1 µmol/L, LY83583 does not itself alter vascular tension20,36 (and see Figure 6A), but like SPC it substantially enhanced the response to depolarization with ∼25 mmol/L [K+] in both MA and IPA (Figure 6A and B; P < 0.001). In contrast to SPC, however, the effects were not significantly inhibited by Gö6983, PP2, or VAS2870 (Figure 6B), consistent with ROS being downstream of PKCε- and Src-mediated activation of NOX1.Figure 6

Bottom Line: At lower concentrations (≤1 µmol/L), however, it does not constrict intrapulmonary arteries (IPAs), but strongly potentiates vasoreactivity.The intracellular superoxide generator LY83583 mimicked the effect of SPC.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