Calcium Mobilization Evoked by Hepatocellular Swelling Is Linked to Activation of Phospholipase Cγ

Moore, Ann L.; Roe, Michael W.; Melnick, Richard F.; Lidofsky, Steven D.

doi:10.1074/jbc.m205945200

Cited by 33 publications

(36 citation statements)

References 37 publications

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“…Neither can we exclude the possibility that product(s) of phospholipase C (PLC)-mediated PIP 2 hydrolysis, such as diacylglycerol or inositol 1,4,5-trisphosphate exert such a role. Interestingly, PLC is activated by hepatocellular swelling (1,32). The present study was therefore designed to explore the role of the PIP 2 /PLC signaling pathway in the modulation of resting and swelling-activated KCNQ1-like K ϩ currents in short-term cultured rat hepatocytes and to determine whether these channels contribute to RVD-induced whole organ K ϩ flux in the intact liver.…”

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confidence: 99%

Modulation of hepatocellular swelling-activated K⁺ currents by phosphoinositide pathway-dependent protein kinase C

Wang¹,

Hill²

2006

American Journal of Physiology-Cell Physiology

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K+ channels participate in the regulatory volume decrease (RVD) accompanying hepatocellular nutrient uptake and bile formation. We recently identified KCNQ1 as a molecular candidate for a significant fraction of the hepatocellular swelling-activated K+ current ( IKVol). We have shown that the KCNQ1 inhibitor chromanol 293B significantly inhibited RVD-associated K+ flux in isolated perfused rat liver and used patch-clamp techniques to define the signaling pathway linking swelling to IKVol activation. Patch-electrode dialysis of hepatocytes with solutions that maintain or increase phosphatidylinositol 4,5-bisphosphate (PIP2) increased IKVol, whereas conditions that decrease cellular PIP2 decreased IKVol. GTP and AlF4− stimulated IKVol development, suggesting a role for G proteins and phospholipase C (PLC). Supporting this, the PLC blocker U-73122 decreased IKVol and inhibited the stimulatory response to PIP2 or GTP. Protein kinase C (PKC) is involved, because K+ current was enhanced by 1-oleoyl-2-acetyl- sn-glycerol and inhibited after chronic PKC stimulation with phorbol 12-myristate 13-acetate (PMA) or the PKC inhibitor GF 109203X. Both IKVol and the accompanying membrane capacitance increase were blocked by cytochalasin D or GF 109203X. Acute PMA did not eliminate the cytochalasin D inhibition, suggesting that PKC-mediated IKVol activation involves the cytoskeleton. Under isotonic conditions, a slowly developing K+ current similar to IKVol was activated by PIP2, lipid phosphatase inhibitors to counter PIP2 depletion, a PLC-coupled α1-adrenoceptor agonist, or PKC activators and was depressed by PKC inhibition, suggesting that hypotonicity is one of a set of stimuli that can activate IKVol through a PIP2/PKC-dependent pathway. The results indicate that PIP2 indirectly activates hepatocellular KCNQ1-like channels via cytoskeletal rearrangement involving PKC activation.

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confidence: 99%

Modulation of hepatocellular swelling-activated K⁺ currents by phosphoinositide pathway-dependent protein kinase C

Wang¹,

Hill²

2006

American Journal of Physiology-Cell Physiology

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“…PLA 2 and Src kinase have also been implicated in the activation of TRPCmediated SOC and ROC activities (Hisatsune et al 2004;Bolotina and Csutora 2005;Vazquez et al 2004b). There is also evidence that indicates PLC may be MS (Brophy et al 1993), with some reports indicating that the mechanosensitivity depends upon Ca 2+ influx (Basavappa et al 1988;Matsumoto et al 1995;Ryan et al 2000;Ruwhof et al 2001;Alexander et al 2004) and others indicating independence of external Ca 2+ and Ca 2+ influx (Mitchell et al 1997;Rosales et al 1997;Moore et al 2002). In either case, the combined evidence indicates that mechanical forces transduced by MscCa and/or by MS enzymes may modulate the gating of all TRP channels.…”

Section: Discussionmentioning

confidence: 87%

“…However, while there are reports that PLC can be mechanically stimulated independent of external Ca 2+ (Rosales et al 1997;Mitchell et al 1997;Moore et al 2002), there are more cases that indicate that the mechanosensitivity of PLC derives from stimulation by Ca 2+ influx via MscCa (Matsumoto et al 1995;Ryan et al 2000;Ruwhof et al 2001). In this case, it becomes important to demonstrate that TRPC6 can be mechanically activated in the absence of external Ca 2+ (e.g., using Ba…”

Section: Trpc6 Role In Myogenic Tonementioning

confidence: 99%

The Mechanosensitive Ca2+ Channel as a Central Regular of Prostate Tumor Cell Migration and Invasiveness

Hamill¹

2011

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY)2. REPORT TYPE 3. DATES COVERED (From -To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail:5f. WORK UNIT NUMBER 4 Introduction A major challenge for treating prostate cancer (PC) is to discover new therapies that will prevent the spread of PC cells from the prostate to distal sites. Our research focuses on the stretch-activated mechanosensitive Ca 2+ permeant channel (MscCa) as a central regulator of prostate tumor cell migration. Our experiments are designed to address the two most basic issues of the disease: the mechanism(s) that trigger progression of PC to malignancy and the urgent need for new therapeutic targets to block or reverse this progression. Our original experiments funded by DOD were aimed to test whether MscCa is expressed in human prostate tumor cells and whether MscCa activity is required for prostate tumor cell migration. We confirmed both results. In the course of these experiments we also discovered that the predominate gating mode of the MscCa differs between noninvasive and invasive PC cells, may be the most powerful determinate of the [Ca 2+ ]i dynamics required to coordinate cell locomotion. The aims of the current award were three-fold. First, determine the mechanisms underlying MscCa gating. Second, determine the cancer-related processes that switch MscCa gating, and third determine whether anti-MscCa conditions that suppress PC migration in vitro also block PC cell invasion in vivo. Insights into these aspects would provide added motivation for developing more selective therapies that target MscCa and its regulatory mechanisms. The basic results supporting our hypothesis have been published (Maroto, R. & Hamill, O.P. MscCa regulation of tumor cell migration and metastasis. Current Topics in Membranes.59, 485-509, 2007). Also included in the Appendix are other manuscripts and abstracts Gotlieb et al., 2008; Maroto & Hamill, 2011; and Maroto, Kurosky and Hamill, 2011) that include specific results described in body of the text. PERFORMING ORGANIZATION NAME(S) AND AD...

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“…In this model, we propose that cells subjected to a high osmotic imbalance generate H 2 O 2 upon NAD(P)H oxidase activation (22) promoting Src-mediated PLC␥1 phosphorylation (10,24) leading to IP 3 -sensitive intracellular Ca 2ϩ mobilization (18,51) and subsequent VSOR Cl Ϫ channel activation. On the other hand, cell swelling triggers the release of ATP (23,33), which in turn acts on P2X4 receptors increasing the Ca 2ϩ permeability and thus, modulating the time course of VSOR Cl Ϫ currents (this work).…”

Section: Vsor CLmentioning

confidence: 99%

“…In the same cells, it has been observed that after exposure to a hypotonic solution, these cells respond with a transient increase in NAD(P)H oxidase-dependent H 2 O 2 production (22), [Ca 2ϩ ] i (18) and release of ATP (23). The [Ca 2ϩ ] i increase in these cells induced by extracellular exposure to hypotonicity was demonstrated to be mediated by PLC␥1 phosphorylation (10). More recently, we established in the same cell system that exogenous application of H 2 O 2 induced PLC␥1 phosphorylation in isotonic conditions.…”

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confidence: 99%

P2X4 Activation Modulates Volume-sensitive Outwardly Rectifying Chloride Channels in Rat Hepatoma Cells

Varela

Penna

Simón

et al. 2010

Journal of Biological Chemistry

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Volume-sensitive outwardly rectifying (VSOR) ClVolume-sensitive outwardly rectifying (VSOR) 2 Cl Ϫ channels are ubiquitously expressed in most mammalian cells types playing a central role in maintaining normal cell volume. However, increasing evidence supports the notion that these channels participate in several other physiological processes, such as salt transport and metabolic stress, apoptosis, proliferation, migration, and cell cycle regulation (1-5). Furthermore, it has also been suggested that a failure in the activation of these channels upon cell swelling is involved in necrotic cell death (6). VSOR Cl Ϫ currents have been well studied and characterized; however, intracellular signal transduction pathways responsible for VSOR Cl Ϫ channel activation in these diverse physiological circumstances remain less understood and appear to be rather contradictory (7). The mechanisms of activation and regulation of VSOR Cl Ϫ channels comprise, depending on the cell type studied, a large variety of factors including ionic strength, macromolecular crowding, intracellular Ca 2ϩ , G proteins, arachidonic acid, and metabolites, protein kinase C, ATP release, ROS production, cytoskeleton proteins, tyrosine kinase-mediated phosphorylation of several proteins, and inactivation of phosphatases (2, 8 -14).Nonetheless, the precise roles of these swelling-induced cellular responses on the activation of VSOR Cl Ϫ channels are not completely identified. In addition, it is evident that they depend on the cell type studied (8). Participation of intracellular Ca 2ϩ in VSOR Cl Ϫ channel activation exemplifies this issue. In bovine pulmonary artery cells, hypotonicity-activated Cl Ϫ currents were found to be already maximally activated at 50 -100 nM [Ca 2ϩ ] i (15), and in Ehrlich ascites tumor cells 25 nM [Ca 2ϩ ] i was reported to be sufficient (16). In contrast, in a rat hepatoma cell line (17) (HTC), it was demonstrated that hypotonicityinduced cell swelling elicits an increase in [Ca 2ϩ ] i , which proved necessary for volume recovery (18).On the other hand, extracellular Ca 2ϩ (Ca o 2ϩ ) has been shown to be fundamental in mouse kidney proximal tubular cells (19), whereas in astrocytes the current development was found to be independent of Ca o 2ϩ (20

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Calcium Mobilization Evoked by Hepatocellular Swelling Is Linked to Activation of Phospholipase Cγ

Abstract: Recovery from swelling of hepatocytes and selected other epithelia is triggered by intracellular Ca 2؉ release from the endoplasmic reticulum, which leads to fluid and electrolyte efflux through volume-sensitive K ؉ and Cl ؊ channels. The aim of this study was to determine the

Cited by 33 publications

References 37 publications

Modulation of hepatocellular swelling-activated K⁺ currents by phosphoinositide pathway-dependent protein kinase C

Modulation of hepatocellular swelling-activated K⁺ currents by phosphoinositide pathway-dependent protein kinase C

The Mechanosensitive Ca2+ Channel as a Central Regular of Prostate Tumor Cell Migration and Invasiveness

P2X4 Activation Modulates Volume-sensitive Outwardly Rectifying Chloride Channels in Rat Hepatoma Cells

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Calcium Mobilization Evoked by Hepatocellular Swelling Is Linked to Activation of Phospholipase Cγ

Abstract: Recovery from swelling of hepatocytes and selected other epithelia is triggered by intracellular Ca 2؉ release from the endoplasmic reticulum, which leads to fluid and electrolyte efflux through volume-sensitive K ؉ and Cl ؊ channels. The aim of this study was to determine the

Cited by 33 publications

References 37 publications

Modulation of hepatocellular swelling-activated K+ currents by phosphoinositide pathway-dependent protein kinase C

Modulation of hepatocellular swelling-activated K+ currents by phosphoinositide pathway-dependent protein kinase C

The Mechanosensitive Ca2+ Channel as a Central Regular of Prostate Tumor Cell Migration and Invasiveness

P2X4 Activation Modulates Volume-sensitive Outwardly Rectifying Chloride Channels in Rat Hepatoma Cells

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Modulation of hepatocellular swelling-activated K⁺ currents by phosphoinositide pathway-dependent protein kinase C

Modulation of hepatocellular swelling-activated K⁺ currents by phosphoinositide pathway-dependent protein kinase C