TRPC1/TRPC3 channels mediate lysophosphatidylcholine-induced apoptosis in cultured human coronary artery smooth
Yuan Wang1,2, Yan Wang1, Gui-Rong Li1,2
1Xiamen Cardiovascular Hospital, Medical School of Xiamen University, Xiamen, Fujian, China.
Abstract:
The earlier study showed that lysophosphatidylcholine (lysoPC) induced apoptosis in human coronary artery smooth muscle cells (SMCs); however, the related molecular mechanisms are not fully understood. The present study investigated how lysoPC induces apoptosis in cultured human coronary artery SMCs using cell viability assay, flow cytometry, confocal microscopy, and molecular biological approaches. We found that lysoPC reduced cell viability in human coronary artery SMCs by eliciting a remarkable Ca2+ influx. The effect was antagonized by La3+, SKF-96365, or Pyr3 as well as by silencing TRPC1 or TRPC3. Co-immunoprecipitation revealed that TRPC1 and TRPC3 had protein-protein interaction. Silencing TRPC1 or TRPC3 countered the lysoPC-induced increase of Ca2+ influx and apoptosis, and the pro-apoptotic proteins Bax and cleaved caspase-3 and decrease of the anti-apoptotic protein Bcl-2 and the survival kinase pAkt. These results demonstrate the novel information that TRPC1/TRPC3 channels mediate lysoPC-induced Ca2+ influx and apoptosis via activating the pro-apoptotic proteins Bax and cleaved caspase-3 and inhibiting the anti-apoptotic protein Bcl-2 and the survival kinase pAkt in human coronary artery SMCs, which implies that TRPC1/TRC3 channels may be the therapeutic target of lysoPC-induced disorders such as atherosclerosis.
Insights
Lysophosphatidylcholine (lysoPC) triggers apoptosis in human coronary artery smooth muscle cells by increasing calcium influx through TRPC1/TRPC3 channels. These channels are potential therapeutic targets for lysoPC-related disorders like atherosclerosis.
Area of Science:
- Cardiovascular Biology
- Cellular Mechanisms
- Molecular Pharmacology
Background:
- Lysophosphatidylcholine (lysoPC) is known to induce apoptosis in human coronary artery smooth muscle cells (SMCs).
- The precise molecular pathways underlying lysoPC-induced apoptosis in SMCs remain incompletely elucidated.
Purpose of the Study:
- To investigate the mechanisms by which lysoPC induces apoptosis in cultured human coronary artery SMCs.
- To identify the role of calcium (Ca2+) influx and specific ion channels in this process.
Main Methods:
- Cell viability assays, flow cytometry, and confocal microscopy were employed.
- Molecular approaches included co-immunoprecipitation and gene silencing (TRPC1/TRPC3).
- Analysis of apoptosis-related proteins (Bax, Bcl-2, cleaved caspase-3) and survival kinase (pAkt) was performed.
Main Results:
- lysoPC significantly reduced SMC viability by inducing substantial Ca2+ influx, which was blocked by TRPC channel inhibitors and silencing of TRPC1 or TRPC3.
- TRPC1 and TRPC3 were found to interact at the protein level.
- Silencing TRPC1/TRPC3 attenuated lysoPC-induced Ca2+ influx, apoptosis, and modulated the expression of Bax, Bcl-2, cleaved caspase-3, and pAkt.
Conclusions:
- TRPC1/TRPC3 channels are critical mediators of lysoPC-induced Ca2+ influx and apoptosis in human coronary artery SMCs.
- These channels regulate apoptosis by affecting the balance of pro-apoptotic (Bax, cleaved caspase-3) and anti-apoptotic (Bcl-2) proteins, as well as the survival kinase pAkt.
- TRPC1/TRPC3 channels represent a potential therapeutic target for managing lysoPC-associated vascular diseases, including atherosclerosis.
More Related Videos
Related Concept Videos
01:09GPCRs Regulate Adenylyl Cylase Activity
01:17The Extrinsic Apoptotic Pathway