DEGs resulting from activating L-type calcium channel, CaV1.2, in mouse valvular interstitial cells (mVICs).
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE151520 | GEO | 2021/06/01
REPOSITORIES: GEO
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Project description:DEGs resulting from activating L-type calcium channel, CaV1.2, in mouse valvular interstitial cells (mVICs).
| PRJNA636195 | ENA
Project description:Increased cardiac contractility during fight-or-flight response is caused by b-adrenergic augmentation of CaV1.2 channels. It is assumed that this iconic regulation involves phosphorylation of CaV1.2 a1/b-subunits. In transgenic murine hearts expressing fully PKA phosphorylation-deficient mutant a1C/b, this regulation persists, however, suggesting involvement of extra-channel factors. We here show that PKA up-regulates cardiac CaV1.2 channels by phosphorylating the small G-protein Rad, relieving constitutive inhibition of CaV1.2. Peroxidase-catalyzed labeling in mice hearts expressing ascorbate peroxidase conjugated-a1C or b2b with multiplexed quantitative proteomics allowed tracking of thousands of proteins in proximity of CaV1.2.
2019-11-19 | PXD014500 | Pride
Project description:Increased cardiac contractility during fight-or-flight response is caused by b-adrenergic augmentation of CaV1.2 channels. It is assumed that this iconic regulation involves phosphorylation of CaV1.2 a1/b-subunits. In transgenic murine hearts expressing fully PKA phosphorylation-deficient mutant a1C/b, this regulation persists, however, suggesting involvement of extra-channel factors. We here show that PKA up-regulates cardiac CaV1.2 channels by phosphorylating the small G-protein Rad, relieving constitutive inhibition of CaV1.2. Peroxidase-catalyzed labeling in mice hearts expressing ascorbate peroxidase conjugated-a1C or b2b with multiplexed quantitative proteomics allowed tracking of thousands of proteins in proximity of CaV1.2.
2019-11-19 | PXD014499 | Pride
Project description:Increased cardiac contractility during fight-or-flight response is caused by b-adrenergic augmentation of CaV1.2 channels. It is assumed that this iconic regulation involves phosphorylation of CaV1.2 a1/b-subunits. In transgenic murine hearts expressing fully PKA phosphorylation-deficient mutant a1C/b, this regulation persists, however, suggesting involvement of extra-channel factors. We here show that PKA up-regulates cardiac CaV1.2 channels by phosphorylating the small G-protein Rad, relieving constitutive inhibition of CaV1.2. Peroxidase-catalyzed labeling in mice hearts expressing ascorbate peroxidase conjugated-a1C or b2b with multiplexed quantitative proteomics allowed tracking of thousands of proteins in proximity of CaV1.2.
2019-11-19 | PXD014501 | Pride
Project description:We performed RNA-Seq analysis of neoatal rat ventricular cardiomyocytes (NRVCs) and human pluripotent stem cells derived cardiomyocytes (hPSC-CMs) which were treated with Nimodipine (NM) to investigate the moleclular mechanism of inhibiting L-type calcium channel (LTCC) to promote cardiomyocyte proliferation.
2022-10-10 | GSE185542 | GEO
Project description:Defective ion channel turnover and clearance of damaged proteins are associated with aging and neurodegeneration. The L-type CaV1.2 voltage-gated calcium channel mediate depolarization-induced calcium signals in heart and brain. Here, we determined the interaction surface between the L-type calcium channel CaVβ subunit and actin using cross-linking mass spectrometry and protein-protein docking, and uncovered a role in replenishing damaged CaV1.2 channels. Computational and in vitro mutagenesis identified hotspots in CaVβ that decrease its affinity for actin but not for CaV1.2. Coexpression of an actin-association-deficient CaVβ mutant with the CaV1.2 channel downregulated current amplitudes with a concomitant reduction in the number of functionally available channels. Neither alterations in the single-channel properties nor changes in the total number of channels at the cell surface were found, indicating that current inhibition resulted from a build-up of conduction-defective channels. Our findings established CaVβ–actin interaction as a key player for selective monitoring and clearing corrupted CaV proteins to ensure the maintenance of a functional pool of channels and proper calcium signal transduction. The CaVβ–actin molecular model introduces a potentially druggable protein-protein interface to intervene CaV-mediated signaling processes.
2024-02-16 | PXD044723 | Pride
Project description:Defective ion channel turnover and clearance of damaged proteins are associated with aging and neurodegeneration. The L-type CaV1.2 voltage-gated calcium channel mediate depolarization-induced calcium signals in heart and brain. Here, we determined the interaction surface between the L-type calcium channel CaVβ subunit and actin using cross-linking mass spectrometry and protein-protein docking, and uncovered a role in replenishing damaged CaV1.2 channels. Computational and in vitro mutagenesis identified hotspots in CaVβ that decrease its affinity for actin but not for CaV1.2. Coexpression of an actin-association-deficient CaVβ mutant with the CaV1.2 channel downregulated current amplitudes with a concomitant reduction in the number of functionally available channels. Neither alterations in the single-channel properties nor changes in the total number of channels at the cell surface were found, indicating that current inhibition resulted from a build-up of conduction-defective channels. Our findings established CaVβ–actin interaction as a key player for selective monitoring and clearing corrupted CaV proteins to ensure the maintenance of a functional pool of channels and proper calcium signal transduction. The CaVβ–actin molecular model introduces a potentially druggable protein-protein interface to intervene CaV-mediated signaling processes.
2024-02-16 | PXD044630 | Pride
Project description:BackgroundCalcific aortic valve disease (CAVD) is the most common heart valve disease in the Western world. We previously proposed that valvular endothelial cells (VECs) replenish injured adult valve leaflets via endothelial-to-mesenchymal transformation (EndMT); however, whether EndMT contributes to valvular calcification is unknown. We hypothesized that aortic VECs undergo osteogenic differentiation via an EndMT process that can be inhibited by valvular interstitial cells (VICs).Approach and resultsVEC clones underwent TGF-β1-mediated EndMT, shown by significantly increased mRNA expression of the EndMT markers α-SMA (5.3 ± 1.2), MMP-2 (13.5 ± 0.6) and Slug (12 ± 2.1) (p < 0.05), (compared to unstimulated controls). To study the effects of VIC on VEC EndMT, clonal populations of VICs were derived from the same valve leaflets, placed in co-culture with VECs, and grown in control/TGF-β1 supplemented media. In the presence of VICs, EndMT was inhibited, shown by decreased mRNA expression of α-SMA (0.1 ± 0.5), MMP-2 (0.1 ± 0.1), and Slug (0.2 ± 0.2) (p < 0.05). When cultured in osteogenic media, VECs demonstrated osteogenic changes confirmed by increase in mRNA expression of osteocalcin (8.6 ± 1.3), osteopontin (3.7 ± 0.3), and Runx2 (5.5 ± 1.5). The VIC presence inhibited VEC osteogenesis, demonstrated by decreased expression of osteocalcin (0.4 ± 0.1) and osteopontin (0.2 ± 0.1) (p < 0.05). Time course analysis suggested that EndMT precedes osteogenesis, shown by an initial increase of α-SMA and MMP-2 (day 7), followed by an increase of osteopontin and osteocalcin (day 14).ConclusionsThe data indicate that EndMT may precede VEC osteogenesis. This study shows that VICs inhibit VEC EndMT and osteogenesis, indicating the importance of VEC-VIC interactions in valve homeostasis.
| S-EPMC4546848 | biostudies-literature
Project description:Differential expression of antiviral factors in H9c2 cells overexpressing Cacnb4 of the Cav1.2 channel
| PRJNA506992 | ENA
Project description:The role viscoelasticity in fibrotic disease progression is an emerging area of interest. Here, a fast-relaxing hydrogel system is exploited to investigate potential crosstalk between calcium signaling and mechanotransduction. Poly(ethylene glycol) (PEG) hydrogels containing boronate and triazole crosslinkers are synthesized, with varying ratios of boronate to triazole crosslinks to systematically vary the extent of stress relaxation. Valvular interstitial cells (VICs) encapsulated in hydrogels with the highest levels of stress relaxation (90%) exhibit a spread morphology by day 1 and are highly aligned (80 ± 2%) by day 5. Key myofibroblast markers, including α-smooth muscle actin (αSMA) and collagen 1a1 (COL1A1), are significantly elevated. VIC myofibroblast activation decreases by 42 ± 18% through inhibition of mechanotransduction, independently of VIC morphology and alignment. Calcium signaling through a transient receptor potential vanilloid 4 (TRPV4) is found to regulate VIC spreading, alignment, and activation in a time dependent manner. Inhibition of calcium signaling at early time points results in disturbed cell alignment, decreased mechanotransduction, and diminished activation, while inhibition at later time points only causes partially reduced myofibroblast activation. These results suggest a potential crosstalk mechanism, where calcium signaling acts upstream of mechanosensing and can regulate VIC myofibroblast activation independently of mechanotransduction.
| S-EPMC7773027 | biostudies-literature