Ca2+ Entry via TRPC Channels Is Necessary for Thrombin-induced NF-κB Activation in Endothelial Cells through AMP-activated Protein Kinase and Protein Kinase Cδ

Bair, Angela M.; Thippegowda, Prabhakar B.; Freichel, Marc; Cheng, Ni; Ye, Richard D.; Vogel, Stephen M.; Yu, Yanni; Flockerzi, Veit; Malik, Asrar B.; Tiruppathì, Chinnaswamy

doi:10.1074/jbc.m803984200

Cited by 75 publications

(66 citation statements)

References 55 publications

(110 reference statements)

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“…The deduced STIM1 sequence revealed the presence of 10 putative phosphorylation sites for p38 MAPK. In recent studies, we showed that SOCE activates the CaMKK␤-AMPK-p38 MAPK signaling pathway in endothelial cells (15). Thus, we tested the postulate that PAR-1-induced SOCE signaling is essential for Ser phosphorylation of STIM1 and subsequent inhibition of SOCE in endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…We have shown that SOCE induced by thrombin ligation of PAR-1 mediates vascular barrier dysfunction and amplifies the expression of inflammatory genes in endothelial cells (3,15,16,32,33). Recent studies have shown that STIM1 is crucial for the activation of SOCE in endothelial cells (3)(4)(5).…”

Section: Discussionmentioning

confidence: 99%

“…Ca 2ϩ Entry-CaMKK␤-AMPK␣1 Axis Signaling Is Required to Activate p38␤ MAPK and STIM1 Phosphorylation-We have shown that Ca 2ϩ entry through TRPC channels activates the CaMKK␤-AMPK-p38 signaling pathway in human pulmonary artery endothelial cells (15). In this study, we exposed (10 M) were used to measure thrombin-induced Ca 2ϩ entry as described above.…”

Section: Pharmacological Activation Of Ampk Induces Stim1 Phosphorylamentioning

confidence: 99%

“…Microvessel Permeability-Studies from our laboratory (15) and others (22) showed that Ca 2ϩ entry signal activates AMPK in endothelial cells. Therefore, we tested whether AMPK signaling is involved in modulating SOCE in endothelial cells.…”

Section: Pharmacological Activation Of Ampk Induces Stim1 Phosphorylamentioning

confidence: 99%

“…In recent studies, we have shown that SOCE induced by thrombin resulted in activation of AMPK and its downstream target p38 MAPK in endothelial cells (15). Thus, we addressed the possibility that SOCE-activated AMPK-p38 MAPK signaling axis is involved in inhibiting SOCE in endothelial cells.…”

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confidence: 99%

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Store-operated Ca2+ Entry (SOCE) Induced by Protease-activated Receptor-1 Mediates STIM1 Protein Phosphorylation to Inhibit SOCE in Endothelial Cells through AMP-activated Protein Kinase and p38β Mitogen-activated Protein Kinase

Sundivakkam

Natarajan

Malik

et al. 2013

Journal of Biological Chemistry

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The Ca2+ sensor STIM1 is crucial for activation of store-operated Ca2+ entry (SOCE) through transient receptor potential canonical and Orai channels. STIM1 phosphorylation serves as an “off switch” for SOCE. However, the signaling pathway for STIM1 phosphorylation is unknown. Here, we show that SOCE activates AMP-activated protein kinase (AMPK); its effector p38β mitogen-activated protein kinase (p38β MAPK) phosphorylates STIM1, thus inhibiting SOCE in human lung microvascular endothelial cells. Activation of AMPK using 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) resulted in STIM1 phosphorylation on serine residues and prevented protease-activated receptor-1 (PAR-1)-induced Ca2+ entry. Furthermore, AICAR pretreatment blocked PAR-1-induced increase in the permeability of mouse lung microvessels. Activation of SOCE with thrombin caused phosphorylation of isoform α1 but not α2 of the AMPK catalytic subunit. Moreover, knockdown of AMPKα1 augmented SOCE induced by thrombin. Interestingly, SB203580, a selective inhibitor of p38 MAPK, blocked STIM1 phosphorylation and led to sustained STIM1-puncta formation and Ca2+ entry. Of the three p38 MAPK isoforms expressed in endothelial cells, p38β knockdown prevented PAR-1-mediated STIM1 phosphorylation and potentiated SOCE. In addition, inhibition of the SOCE downstream target CaM kinase kinase β (CaMKKβ) or knockdown of AMPKα1 suppressed PAR-1-mediated phosphorylation of p38β and hence STIM1. Thus, our findings demonstrate that SOCE activates CaMKKβ-AMPKα1-p38β MAPK signaling to phosphorylate STIM1, thereby suppressing endothelial SOCE and permeability responses.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Pharmacological Activation Of Ampk Induces Stim1 Phosphorylamentioning

confidence: 99%

Section: Pharmacological Activation Of Ampk Induces Stim1 Phosphorylamentioning

confidence: 99%

mentioning

confidence: 99%

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Store-operated Ca2+ Entry (SOCE) Induced by Protease-activated Receptor-1 Mediates STIM1 Protein Phosphorylation to Inhibit SOCE in Endothelial Cells through AMP-activated Protein Kinase and p38β Mitogen-activated Protein Kinase

Sundivakkam

Natarajan

Malik

et al. 2013

Journal of Biological Chemistry

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Effect and mechanism of transient receptor potential canonical channel 3 on hyperoxic lung injury in neonatal rats

Fu,

Gong,

et al. 2024

Pediatric Discovery

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The aim of this study is to research the expression of the transient receptor potential canonical channel 3 (TRPC3) in a neonatal hyperoxic lung injury model of bronchopulmonary dysplasia (BPD), and to further investigate the role of the TRPC3/nuclear factor‐κB (NF‐κB) signaling pathway in hyperoxia‐induced BPD by a TRPC3 agonist (GSK1702934A). The hyperoxic lung injury model of BPD was established in Sprague–Dawley neonatal rats. Hematoxylin and eosin (HE) staining and radial alveolar count (RAC) values showed that the hyperoxic lung injury model of BPD was successfully established in the neonatal rats, and pulmonary edema was found in the neonatal rats with BPD. The results of reference transcriptome sequencing, Quantitative real‐time PCR (qPCR), and western blot showed lower pulmonary expression of TRPC3 in the BPD group than in the control group. Immunofluorescence showed predominant expression of TRPC3 in airways and pulmonary vessels, and the fluorescence intensity of the BPD group was lower than that of the control group. Lung dry‐to‐wet weight ratio, HE staining, and RAC value showed that the lung histomorphology significantly improved in the BPD + TRPC3 agonist group compared with the BPD group on day 14 but did not revert to the level of the control group. According to qPCR results, compared with the control group, the expression of NF‐κB1 decreased and the expression of NF‐κBiz increased in the BPD group, whereas the expression of NF‐κBiz decreased in the BPD + TRPC3 agonist group. Therefore, we draw the conclusion that TRPC3 may activate NF‐κB by inhibiting NF‐κBiz to promote cell proliferation and lung growth and development.

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Caveolae and Signaling in Pulmonary Vascular Endothelial and Smooth Muscle Cells

Amerongen

Minshall²,

Malik³

2010

Textbook of Pulmonary Vascular Disease

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Ca2+ Entry via TRPC Channels Is Necessary for Thrombin-induced NF-κB Activation in Endothelial Cells through AMP-activated Protein Kinase and Protein Kinase Cδ

Cited by 75 publications

References 55 publications

Store-operated Ca2+ Entry (SOCE) Induced by Protease-activated Receptor-1 Mediates STIM1 Protein Phosphorylation to Inhibit SOCE in Endothelial Cells through AMP-activated Protein Kinase and p38β Mitogen-activated Protein Kinase

Store-operated Ca2+ Entry (SOCE) Induced by Protease-activated Receptor-1 Mediates STIM1 Protein Phosphorylation to Inhibit SOCE in Endothelial Cells through AMP-activated Protein Kinase and p38β Mitogen-activated Protein Kinase

Effect and mechanism of transient receptor potential canonical channel 3 on hyperoxic lung injury in neonatal rats

Caveolae and Signaling in Pulmonary Vascular Endothelial and Smooth Muscle Cells

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