Ca2+ Influx Induced by Protease-activated Receptor-1 Activates a Feed-forward Mechanism of TRPC1 Expression via Nuclear Factor-κB Activation in Endothelial Cells

Paria, Biman C.; Bair, Angela M.; Xue, Jiaping; Yu, Yanni; Malik, Asrar B.; Tiruppathì, Chinnaswamy

doi:10.1074/jbc.m600722200

Cited by 60 publications

(58 citation statements)

References 47 publications

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“…Expression of TRPC1 was also evaluated in the presence of NF-B inhibitor, which showed that addition of NF-B inhibitor significantly decreases TRPC1 protein levels, but not SERCA2 levels ( Figure 7D). This supports the finding that TRPC1 promoter has NF-B responsive elements and that its expression is dependent on NF-B transactivation (Paria et al, 2003(Paria et al, , 2006. These results confirm that TRPC1-mediated resistance to thapsigargininduced apoptosis, in part, associates with the activation of the NF-B.…”

supporting

confidence: 79%

Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca²⁺ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease

Pani

Cornatzer²,

Cornatzer

et al. 2006

MBoC

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The mechanism(s) involved in regulation of store operated calcium entry in Darier's disease (DD) is not known. We investigated the distribution and function of transient receptor potential canonical (TRPC) in epidermal skin cells. DD patients demonstrated up-regulation of TRPC1, but not TRPC3, in the squamous layers. Ca 2؉ influx was significantly higher in keratinocytes obtained from DD patients and showed enhanced proliferation compared with normal keratinocytes. Similar up-regulation of TRPC1 was also detected in epidermal layers of SERCA2 ؉/؊ mice. HaCaT cells expressed TRPC1 in the plasma membrane. Expression of sarco(endo)plasmic reticulum Ca 2؉ ATPase (SERCA)2 small interfering RNA (siRNA) in HaCaT cells increased TRPC1 levels and thapsigargin-stimulated Ca 2؉ influx, which was blocked by store-operated calcium entry inhibitors. Thapsigargin-stimulated intracellular Ca 2؉ release was decreased in DD cells. DD keratinocytes exhibited increased cell survival upon thapsigargin treatment. Alternatively, overexpression of TRPC1 or SERCA2-siRNA in HaCaT cells demonstrated resistance to thapsigargin-induced apoptosis. These effects were dependent on external Ca 2؉ and activation of nuclear factor-B. Isotretinoin reduced Ca 2؉ entry in HaCaT cells and decreased survival of HaCaT and DD keratinocytes. These findings put forward a novel consequence of compromised SERCA2 function in DD wherein up-regulation of TRPC1 augments cell proliferation and restrict apoptosis. We suggest that the anti-apoptotic effect of TRPC1 could potentially contribute to abnormal keratosis in DD. INTRODUCTIONDarier's disease (DD) is an autosomal dominant inherited skin disease, which is characterized by the loss of adhesion between epidermal cells and abnormal keratinization (Burge and Wilkinson 1992). Typical histological findings include focal areas of separation between suprabasal epidermal cells, unusual dyskeratosis with round dyskeratotic keratinocytes (Munro, 1992). Mutations in the sarco(endo)plasmic reticulum Ca 2ϩ ATPase (SERCA) isoform 2b (SERCA2b) gene leads to a loss of function, and these mutations have been shown to cause DD (Sakuntabhai et al., 1999). Most physiological systems are able to compensate for the loss of function of SERCA2b, possibly because of expression of other SERCA isoforms within those tissues (Dhitavat et al., 2003;Tavadia et al., 2004). However, of the multiple isoforms of SERCA1, -2, or -3, only SERCA2b is expressed in keratinocytes (Lytton and MacLennan, 1988;Ruiz-Perez et al., 1999). The mutated SERCA2 fails to sequester cytosolic Ca 2ϩ into the endoplasmic reticulum (ER) lumen, thereby disturbing the otherwise normal Ca 2ϩ homeostasis circuitry within the cells (Zhao et al., 2001;Ahn et al., 2003). Although oral retinoids, such as isotretinoin, have been shown to reduce hyperkeratosis (Burge and Wilkinson, 1992), the mechanism behind dysfunction of SERCA2 resulting in keratosis remains elusive.Ca 2ϩ is an integral signaling element that regulates numerous cellular processes (Clapham, 1995;Berridge e...

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confidence: 79%

Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca²⁺ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease

Pani

Cornatzer²,

Cornatzer

et al. 2006

MBoC

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“…We showed that human vascular ECs predominantly express isoform TRPC1 Thippegowda et al, 2010). In addition, we showed that inflammatory mediators can induce the expression of TRPC1 in human vascular ECs via the nuclear factor-B pathway (Paria et al, 2003(Paria et al, , 2004(Paria et al, , 2006. Increased TRPC1 expression was associated with augmented thrombin-induced Ca 2ϩ entry and permeability in-crease in human ECs (Paria et al, 2004).…”

Section: Introductionmentioning

confidence: 82%

The Ca²⁺ Sensor Stromal Interaction Molecule 1 (STIM1) Is Necessary and Sufficient for the Store-Operated Ca²⁺ Entry Function of Transient Receptor Potential Canonical (TRPC) 1 and 4 Channels in Endothelial Cells

et al. 2011

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“…This is reminiscent of studies by Tiruppathi and colleagues showing that tumor necrosis factor-␣ induces NF-B-dependent upregulation of TRPC1 in human umbilical vein endothelial cells (HUVECs) (Paria et al, 2003); thrombin-induced TRPC1 upregulation in HUVECs was attributed to the enhancement of NF-B transcriptional activity by Ca 2ϩ signaling in a feedforward manner and subsequent protein kinase C␣ (PKC␣) activation (Paria et al, 2006). This group has also recently shown that another type of PKC, PKC␦, is important in another type of endothelial cell, the human pulmonary arterial endothelial cell, where thrombin-induced NF-B activation is mediated through Ca 2ϩ entry via TRPC1 and subsequent activation of Ca 2ϩ -independent PKC␦ activation (Bair et al, 2009).…”

Section: Par-1-induced Astrocytic Responsesmentioning

confidence: 91%

Transient Receptor Potential Canonical 3 (TRPC3) Mediates Thrombin-Induced Astrocyte Activation and Upregulates Its Own Expression in Cortical Astrocytes

Shirakawa¹,

Sakimoto²,

Nakao³

et al. 2010

J. Neurosci.

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Reactive astrogliosis, defined by abnormal morphology and excessive cell proliferation, is a characteristic response of astrocytes to CNS injuries, including intracerebral hemorrhage. Thrombin, a major blood-derived serine protease, leaks into the brain parenchyma upon blood-brain barrier disruption and can induce brain injury and astrogliosis. Transient receptor potential canonical (TRPC) channels, Ca 2ϩ -permeable, nonselective cation channels, are expressed in astrocytes and involved in Ca 2ϩ influx after receptor stimulation; however, their pathophysiological functions in reactive astrocytes remain unknown. We investigated the pathophysiological roles of TRPC in thrombin-activated cortical astrocytes. Application of thrombin (1 U/ml, 20 h) upregulated TRPC3 protein, which was associated with increased Ca 2ϩ influx after thapsigargin treatment. Pharmacological manipulations revealed that the TRPC3 upregulation was mediated by protease-activated receptor 1 (PAR-1), extracellular signal-regulated protein kinase, c-Jun NH 2 -terminal kinase, and nuclear factor-B signaling and required de novo protein synthesis. The Ca 2ϩ signaling blockers BAPTA-AM, cyclopiazonic acid, and 2-aminoethoxydiphenyl borate and a selective TRPC3 inhibitor, pyrazole-3, attenuated TRPC3 upregulation, suggesting that Ca 2ϩ signaling through TRPC3 contributes to its increased expression. Thrombin-induced morphological changes at 3 h upregulated S100B, a marker of reactive astrocytes, at 20 h and increased astrocytic proliferation by 72 h, all of which were inhibited by Ca 2ϩ -signaling blockers and specific knockdown of TRPC3 using small interfering RNA. Intracortical injection of SFLLR-NH 2 , a PAR-1 agonist peptide, induced proliferation of astrocytes, most of which were TRPC3 immunopositive. These results suggest that thrombin dynamically upregulates TRPC3 and that TRPC3 contributes to the pathological activation of astrocytes in part through a feedforward upregulation of its own expression.

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Ca2+ Influx Induced by Protease-activated Receptor-1 Activates a Feed-forward Mechanism of TRPC1 Expression via Nuclear Factor-κB Activation in Endothelial Cells

Cited by 60 publications

References 47 publications

Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca²⁺ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease

Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca²⁺ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease

The Ca²⁺ Sensor Stromal Interaction Molecule 1 (STIM1) Is Necessary and Sufficient for the Store-Operated Ca²⁺ Entry Function of Transient Receptor Potential Canonical (TRPC) 1 and 4 Channels in Endothelial Cells

Transient Receptor Potential Canonical 3 (TRPC3) Mediates Thrombin-Induced Astrocyte Activation and Upregulates Its Own Expression in Cortical Astrocytes

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Ca2+ Influx Induced by Protease-activated Receptor-1 Activates a Feed-forward Mechanism of TRPC1 Expression via Nuclear Factor-κB Activation in Endothelial Cells

Cited by 60 publications

References 47 publications

Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca2+ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease

Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca2+ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease

The Ca2+ Sensor Stromal Interaction Molecule 1 (STIM1) Is Necessary and Sufficient for the Store-Operated Ca2+ Entry Function of Transient Receptor Potential Canonical (TRPC) 1 and 4 Channels in Endothelial Cells

Transient Receptor Potential Canonical 3 (TRPC3) Mediates Thrombin-Induced Astrocyte Activation and Upregulates Its Own Expression in Cortical Astrocytes

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Resources

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Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca²⁺ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease

Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca²⁺ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease

The Ca²⁺ Sensor Stromal Interaction Molecule 1 (STIM1) Is Necessary and Sufficient for the Store-Operated Ca²⁺ Entry Function of Transient Receptor Potential Canonical (TRPC) 1 and 4 Channels in Endothelial Cells