Role of Transient Receptor Potential C3 in TNF-α–Enhanced Calcium Influx in Human Airway Myocytes

White, Thomas A.; Xue, Ailing; Chini, Eduardo N.; Thompson, Michael A.; Sieck, Gary C.; Wylam, Mark E.

doi:10.1165/rcmb.2006-0003oc

Cited by 121 publications

(130 citation statements)

References 45 publications

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“…Moreover, the increased TRPC3 expression was associated with augmented Ach-elicited calcium responses as well as a sixfold increase in SOCE (32). Transient transfection using small interfering RNA, which decreased TRPC3 expression, also resulted in attenuation of SOCE and agonist-induced [Ca 21 ] i responses (32). These studies provided an additional mechanism of intracellular calcium regulation in ASM cells by the inflammatory cytokine TNF-a involving TRPC3.…”

Section: Inflammatory Cytokines and Cd38/cadpr-mediated Cellular Calcmentioning

confidence: 84%

“…Thus, TRP channel activity may share cross-talk with second messenger systems such as the CD38/cADPR signaling pathway. A study by White and coworkers provided evidence for the expression of multiple TRPC isoforms in human bronchial smooth muscle cells, although TRPC3 appears to be the predominant isoform involved in receptor-and store-operated calcium influx (32). It is worth noting that calcium release through the IP 3 receptor channels is critical for activation of the RyR channels in ASM cells, since blocking IP 3 generation resulted in complete abolition of the calcium response to Ach (13).…”

Section: Cyclic Adp-ribose As An Endogenous Ligand For the Ryanodine mentioning

confidence: 99%

“…Further studies demonstrated that the up-regulation of CD38 by TNF-a is mediated through the transcription factors NF-kB and AP-1 and involves the MAP kinases (92,93). White and colleagues reported a significantly increased expression of TRPC3 after TNF-a treatment of ASM cells (32). Moreover, the increased TRPC3 expression was associated with augmented Ach-elicited calcium responses as well as a sixfold increase in SOCE (32).…”

Section: Inflammatory Cytokines and Cd38/cadpr-mediated Cellular Calcmentioning

confidence: 99%

“…White and colleagues reported a significantly increased expression of TRPC3 after TNF-a treatment of ASM cells (32). Moreover, the increased TRPC3 expression was associated with augmented Ach-elicited calcium responses as well as a sixfold increase in SOCE (32). Transient transfection using small interfering RNA, which decreased TRPC3 expression, also resulted in attenuation of SOCE and agonist-induced [Ca 21 ] i responses (32).…”

Section: Inflammatory Cytokines and Cd38/cadpr-mediated Cellular Calcmentioning

confidence: 99%

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Calcium Signaling in Airway Smooth Muscle

Jude¹,

Wylam²,

Walseth³

et al. 2008

Proceedings of the American Thoracic Society

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Contractility of airway smooth muscle requires elevation of intracellular calcium concentration. Under resting conditions, airway smooth muscle cells maintain a relatively low intracellular calcium concentration, and activation of the surface receptors by contractile agonists results in an elevation of intracellular calcium, culminating in contraction of the cell. The pattern of elevation of intracellular calcium brought about by agonists is a dynamic process and involves the coordinated activities of ion channels located in the plasma membrane and the sarcoplasmic reticulum. Among the signaling molecules involved in this dynamic calcium regulation in airway smooth muscle cells are inositol 1,4,5-trisphosphate and cyclic ADPribose, which mobilize calcium from the sarcoplasmic reticulum by acting via the inositol 1,4,5-trisphosphate and ryanodine receptors, respectively. In addition, calcium influx from the extracellular space is critical for the repletion of the intracellular calcium stores during activation of the cells by agonists. Calcium influx can occur via voltage-and receptor-gated channels in the plasma membrane, as well as by influx that is triggered by depletion of the intracellular stores (i.e., store-operated calcium entry mechanism). Transient receptor potential proteins appear to mediate the calcium influx via receptor-and store-operated channels. Recent studies have shown that proinflammatory cytokines regulate the expression and activity of the pathways involved in intracellular calcium regulation, thereby contributing to airway smooth muscle cell hyperresponsiveness. In this review, we will discuss the specific roles of cyclic ADP-ribose/ryanodine receptor channels and transient receptor potential channels in the regulation of intracellular calcium in airway smooth muscle cells. DYNAMIC INTRACELLULAR CALCIUM REGULATION IN AIRWAY SMOOTH MUSCLE CELLSExposure of airway smooth muscle (ASM) cells to contractile agonists results in a biphasic elevation of intracellular calcium concentration ([Ca 21 ] i ) that is characterized by an initial rapid and transient rise in calcium, followed by a decline to a lower, sustained steady-state concentration above the basal level (1-3). This biphasic [Ca 21 ] i response results from calcium influx from the extracellular space and release of calcium from the intracellular stores (i.e., the sarcoplasmic reticulum [SR]). Earlier studies have attributed the initial rapid and transient phase of the [Ca 21 ] i response to release from the SR, while the sustained phase of the response was thought to be due to influx from the extracellular space (2-6). Recent investigations using the improved temporal and spatial resolution features of real-time confocal microscopy have shed light on the dynamics of the [Ca 21 ] i response in ASM cells. These studies have shown that the biphasic [Ca 21 ] i response of ASM cells elicited by contractile agonists in reality consists of propagating regenerative calcium oscillations that originate at a location within a cell and propagate...

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Section: Inflammatory Cytokines and Cd38/cadpr-mediated Cellular Calcmentioning

confidence: 84%

Section: Cyclic Adp-ribose As An Endogenous Ligand For the Ryanodine mentioning

confidence: 99%

Section: Inflammatory Cytokines and Cd38/cadpr-mediated Cellular Calcmentioning

confidence: 99%

Section: Inflammatory Cytokines and Cd38/cadpr-mediated Cellular Calcmentioning

confidence: 99%

See 2 more Smart Citations

Calcium Signaling in Airway Smooth Muscle

Jude¹,

Wylam²,

Walseth³

et al. 2008

Proceedings of the American Thoracic Society

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“…[241][242][243][244][245][246][247][248] In addition, some somnogenic effectors can activate calpains independently of Ca 2þ transients. For example, EGF can activate calpain-2 by upregulating kinases that phosphorylate and thereby activate this calpain.…”

Section: Relationship Of Protein Fragments To Other Somnogensmentioning

confidence: 99%

Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis

Varshavsky

2012

Protein Science

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Despite extensive understanding of sleep regulation, the molecular-level cause and function of sleep are unknown. I suggest that they originate in individual neurons and stem from increased production of protein fragments during wakefulness. These fragments are transient parts of protein complexes in which the fragments were generated. Neuronal Ca 21 fluxes are higher during wakefulness than during sleep. Subunits of transmembrane channels and other proteins are cleaved by Ca 21 -activated calpains and by other nonprocessive proteases, including caspases and secretases. In the proposed concept, termed the fragment generation (FG) hypothesis, sleep is a state during which the production of fragments is decreased (owing to lower Ca 21 transients) while fragment-destroying pathways are upregulated. These changes facilitate the elimination of fragments and the remodeling of protein complexes in which the fragments resided. The FG hypothesis posits that a proteolytic cleavage, which produces two fragments, can have both deleterious effects and fitness-increasing functions. This (previously not considered) dichotomy can explain both the conservation of cleavage sites in proteins and the evolutionary persistence of sleep, because sleep would counteract deleterious aspects of protein fragments. The FG hypothesis leads to new explanations of sleep phenomena, including a longer sleep after sleep deprivation. Studies in the 1970s showed that ethanol-induced sleep in mice can be strikingly prolonged by intracerebroventricular injections of either Ca 21 alone or Ca 21 and its ionophore (Erickson et al., Science 1978;199:1219-1221 Harris, Pharmacol Biochem Behav 1979;10:527-534; Erickson et al., Pharmacol Biochem Behav 1980;12:651-656). These results, which were never interpreted in connection to protein fragments or the function of sleep, may be accounted for by the FG hypothesis about molecular causation of sleep.

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TRPC3 overexpression and intervention in airway smooth muscle of ovalbumin‐induced hyperresponsiveness and remodeling

Zhang

Wang

et al. 2018

Cell Biology International

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Transient receptor potential canonical channel 3 (TRPC3) proteins function as non-voltage-gated Ca -permeable channels and play divergent roles in many processes of pathophysiology. The purpose of this study was to determine the relationship between TRPC3 expression and airway hyperresponsiveness and remodeling in ovalbumin-induced asthmatic Kunming mice. Mice were sensitized and challenged by ovalbumin to establish asthmatic model. Hematoxylin-eosin staining, hydroxyproline assay, and isometric tracheal ring force measurement were used to evaluate airway remodeling and hyperresponsiveness in asthmatic mice. Western blot was performed to detect the expression of TRPC3 proteins. MTT assay was used to measure the proliferation of airway smooth muscle cells. TRPC3 protein expression increased in airway smooth muscle of asthmatic mice. GdCl , a nonspecific TRPC blocker, attenuated the contractile force of airway smooth muscle. Fetal bovine serum stimulated airway smooth muscle cells proliferation and augmented TRPC3 protein expression. Both TRPC3 blockade by GdCl or specific TRPC3 antibodies and gene silencing by siRNA inhibited the proliferation of airway smooth muscle cells. In contrast, the current drugs treatment for asthma such as Dexamethasone and Aminophylline had no effects on TRPC3 protein overexpression. Therefore, TRPC3 protein overexpression may be involved in airway smooth muscle hyperresponsiveness and remodeling in asthmatic mice, providing evidence for a new direction of asthma pathogenesis research and a new target for drug intervention.

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Role of Transient Receptor Potential C3 in TNF-α–Enhanced Calcium Influx in Human Airway Myocytes

Cited by 121 publications

References 45 publications

Calcium Signaling in Airway Smooth Muscle

Calcium Signaling in Airway Smooth Muscle

Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis

TRPC3 overexpression and intervention in airway smooth muscle of ovalbumin‐induced hyperresponsiveness and remodeling

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