N-acyl dopamines induce cell death in PC12 cell line via induction of nitric oxide generation and oxidative stress

Ashba, A. M.; Akimov, M. G.; Gretskaya, N. M.; Безуглов, В. В.

doi:10.1134/s1607672916020010

Cited by 7 publications

(4 citation statements)

References 9 publications

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“…); however, later, it was found that the active activator of this receptor is alpha-lysophosphatidylinositol (LPI), which is considered the primary natural ligand [ 4 ] of the receptor. We demonstrated that another natural ligand for this receptor can be arachidonoyl dopamine, as well as other acyl dopamines [ 5 , 6 ]. Thus, the GPR55 receptor is currently positioned as a multi-ligand receptor.…”

Section: Introductionmentioning

confidence: 99%

“…As such, LPI induces proliferation [ 16 ] or migration [ 17 ], while anandamide and acyl dopamines induce apoptosis of cancer cells. The exact mechanism of cell death of the latter process may differ, for exam-ple, in the cells of rat pheochromocytoma PC12, acyl dopamines induced the expression of NO synthase, which in turn generated reactive nitrogen and oxygen species as a by-product [ 6 ]. In the case of anandamide in cholangiocarcinoma cells, the death receptor is activated with the participation of GPR55 [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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The Mechanisms of GPR55 Receptor Functional Selectivity during Apoptosis and Proliferation Regulation in Cancer Cells

Akimov

Gretskaya

Dudina

et al. 2023

IJMS

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GPR55 is a non-canonical cannabinoid receptor, important for cancer proliferation. Depending on the ligand, it induces either cell proliferation or death. The objective of the study was to establish the mechanisms of this multidirectional signaling. Using the CRISPR-Cas9 system, the GPR55, CB1, CB2, and GPR18 receptor knockouts of the MDA-MB-231 line were obtained. After the CB2 receptor knockout, the pro-apoptotic activity of the pro-apoptotic ligand docosahexaenoyl dopamine (DHA-DA) slightly increased, while the pro-proliferative activity of the most active synthetic ligand of the GPR55 receptor (ML-184) completely disappeared. On the original cell line, the stimulatory effect of ML-184 was removed by the CB2 receptor blocker and by GPR55 receptor knockout. Thus, it can be confidently assumed that when proliferation is stimulated with the participation of the GPR55 receptor, a signal is transmitted from the CB2 receptor to the GPR55 receptor due to the formation of a heterodimer. GPR18 was additionally involved in the implementation of the pro-apoptotic effect of DHA-DA, while the CB1 receptor is not involved. In the implementation of the pro-apoptotic action of DHA-DA, the elimination of Gα13 led to a decrease in cytotoxicity. The obtained data provide novel details to the mechanism of the pro-proliferative action of GPR55.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Mechanisms of GPR55 Receptor Functional Selectivity during Apoptosis and Proliferation Regulation in Cancer Cells

Akimov

Gretskaya

Dudina

et al. 2023

IJMS

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“…Later, it was found that the active stimulator of this receptor is lysophosphatidylinositol (LPI), which is considered the primary natural ligand [1] of the GPR55 receptor. We have shown that another natural ligand for this receptor can be arachidonoyldopamine, as well as other acyl dopamines [2,3]. Thus, the GPR55 receptor is currently positioned as a multi-ligand receptor.…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, activation of GPR55 by anandamide and acyl dopamines induces cell death via apoptosis. The exact mechanism of implementation of this process may differ: for example, in the cells of rat pheochromocytoma PC12, the expression of NO synthase is stimulated, which synthesizes reactive oxygen species as a by-product [3]. In the case of anandamide in cholangiocarcinoma cells, the death receptor is activated with the participation of GPR55 [8].…”

Section: Introductionmentioning

confidence: 99%

The Mechanisms of GPR55 Receptor Functonal Selectivity

Akimov

Gretskaya

Dudina

et al. 2022

Preprint

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The objective of the project is to establish the mechanisms of multidirectional signal transmission through the same G-protein coupled receptor GPR55. Using the CRISPR-Cas9 system, clones of the MDA-MB-231 line knockout for the GPR55 (3 clones) and CB2 (CNR2 - 6 clones) receptor genes were obtained. On clones of the MDA-MB-231 line with a knockout CB2 receptor, the cytotoxic activity of the pro-apoptotic ligand docosahexaenoyldopamine (DHA-DA) did not change or slightly increased, while the pro-proliferative activity of the most active synthetic ligand of the GPR55 receptor (ML-184) completely disappeared. On the original line MDA-MB-231, the stimulatory effect of ML-184 is removed by the CB2 receptor blocker, but not by GPR55. At the same time, the stimulating effect of ML-184 is practically not manifested on cell lines knockout at the GPR55 receptor. Thus, it can be confidently assumed that when proliferation is stimulated with the participation of the GPR55 receptor, a signal is transmitted from the CB2 receptor to the GPR55 receptor due to the formation of a heterodimer. GPR18 and TRPV1 receptors are additionally involved in the implementation of the cytotoxic effect of DHA-DA, while the CB1 receptor is not involved. In the implementation of the cytotoxic action of DHA-DA, the predominant participation of one of the Ga subunits was not found, but the Ga13 subunit plays a decisive role in the implementation of the proproliferative action. The Gaq subunit is also important, although to a lesser extent than Ga13.

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Selective Action of N-Arachidonoyl Dopamine on Viability and Proliferation of Stromal Cells from Eutopic and Ectopic Endometrium

et al. 2019

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N-acyl dopamines induce cell death in PC12 cell line via induction of nitric oxide generation and oxidative stress

Cited by 7 publications

References 9 publications

The Mechanisms of GPR55 Receptor Functional Selectivity during Apoptosis and Proliferation Regulation in Cancer Cells

The Mechanisms of GPR55 Receptor Functional Selectivity during Apoptosis and Proliferation Regulation in Cancer Cells

The Mechanisms of GPR55 Receptor Functonal Selectivity

Selective Action of N-Arachidonoyl Dopamine on Viability and Proliferation of Stromal Cells from Eutopic and Ectopic Endometrium

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