Cyclic stretch-induced cPLA2 mediates ERK 1/2 signaling in rabbit proximal tubule cells

Alexander, Larry D.; Alagarsamy, Suganthi; Douglas, Janice G.

doi:10.1111/j.1523-1755.2004.00405.x

Cited by 65 publications

(75 citation statements)

References 41 publications

(31 reference statements)

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“…Stretching of kidney epithelial cells has been reported to cause ERK activation as well as proliferation, a crucial factor in cyst development (24,25). Alexander et al (25) recently demonstrated that cyclic stretch activates ERK in rabbit proximal tubule cells by releasing arachidonic acid through calcium channel activation followed by cPLA 2 phosphorylation, and subsequent events involved activation of c-Src and phosphorylation of EGF receptor, leading to ERK activation.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Signal–Regulated Kinase Inhibition Slows Disease Progression in Mice with Polycystic Kidney Disease

Omori¹,

Hida²,

Fujita³

et al. 2006

Journal of the American Society of Nephrology

131

104

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The expression of mitogen-activated protein kinases (MAPK) in DBA/2-pcy/pcy (pcy) mice, a murine model of polycystic kidney disease was investigated. Proliferating cell nuclear antigen-positive cells were recognized in cyst epithelium from embryonic day 14.5 to 25 wk of age. Extracellular signal-regulated kinase (ERK) was expressed in the renal tubules of control and pcy mice, but stronger immunostaining was observed in cyst epithelium. Phosphorylated ERK was detected only in pcy mice and was localized predominantly in the cysts. p38 MAPK (p38) was no longer expressed after birth in controls but was detected in the cyst epithelium and in occasional tubular cells of pcy mice at all stages examined. c-Jun N-terminal kinase (JNK) was expressed in all tubular segments of controls after neonatal day 7, whereas in pcy kidneys, tubules became positive for JNK after 8 wk, and the cysts expressed little JNK. Administration of an oral MAP/ERK kinase inhibitor, PD184352, 400 mg/kg per d, to 10-wk-old pcy mice daily for the first week and then every third day for 6 additional weeks significantly decreased BP, kidney weight, serum creatinine level, and water intake and significantly increased urine osmolality. The cystic index and expression of phosphorylated ERK and ERK were significantly lower in PD184352-treated pcy mice. These results demonstrate that the expression of MAPK is dysregulated in cyst epithelium and that inhibition of ERK slowed the progression of renal disease in pcy mice.

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Section: Discussionmentioning

confidence: 99%

Extracellular Signal–Regulated Kinase Inhibition Slows Disease Progression in Mice with Polycystic Kidney Disease

Omori¹,

Hida²,

Fujita³

et al. 2006

Journal of the American Society of Nephrology

131

104

View full text Add to dashboard Cite

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“…Persistence of the responses, however, in low external Ca 2ϩ argues against Ca 2ϩ entry as the initiating factor in the stretch-dependent responses of ICC-IM. Phospholipase A 2 (PLA 2 ), which liberates arachidonic acid, is mechanosensitive in some cells (46,47). Thus, it is possible that mechanotransduction coupling, linked through activation of PLA 2 , could be a previously unrecognized property of ICC-IM.…”

Section: Discussionmentioning

confidence: 99%

Interstitial cells of Cajal mediate mechanosensitive responses in the stomach

Won

Sanders

Ward

2005

Proc. Natl. Acad. Sci. U.S.A.

152

141

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Changes in motor activity are a basic response to filling of smooth muscle organs. Responses to gastric filling, for example, are thought to be regulated by neural reflexes. Here, we demonstrate a previously uncharacterized aspect of stretch-dependent responses in visceral smooth muscles that is mediated by mechanosensitive interstitial cells of Cajal. Length ramps were applied to the murine antral muscles while recording intracellular electrical activity and isometric force. Stretching muscles by an average of 27 ؎ 1% of resting length resulted in 5 mN of force. Increasing length caused membrane depolarization and increased slow-wave frequency. The responses were dependent on the rate of stretch. Stretch-dependent responses were not inhibited by neuronal antagonists or nifedipine. Increases in slow-wave frequency, but not membrane depolarization, were inhibited by reducing external Ca 2؉ (100 M) and by Ni 2؉ (250 M). Responses to stretch were inhibited by indomethacin (1 M) and were absent in cyclooxygenase II-deficient mice, suggesting that cyclooxygenase II-derived eicosanoids may mediate these responses. Dual microelectrode impalements of muscle cells within the corpus and antrum showed that stretch-induced changes in slow-wave frequency uncoupled proximal-to-distal propagation of slow waves. This uncoupling could interfere with gastric peristalsis and impede gastric emptying. Stretch of antral muscles of W͞W V mice, which lack intramuscular interstitial cells of Cajal, did not affect membrane depolarization or slow-wave frequency. These data demonstrate a previously uncharacterized nonneural stretch reflex in gastric muscles and provide physiological evidence demonstrating a mechanosensitive role for interstitial cells of Cajal in smooth muscle tissues.gastric compliance ͉ pacemaker ͉ stretch ͉ slow waves ͉ propagation

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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: 88%

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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Cyclic stretch-induced cPLA2 mediates ERK 1/2 signaling in rabbit proximal tubule cells

Cited by 65 publications

References 41 publications

Extracellular Signal–Regulated Kinase Inhibition Slows Disease Progression in Mice with Polycystic Kidney Disease

Extracellular Signal–Regulated Kinase Inhibition Slows Disease Progression in Mice with Polycystic Kidney Disease

Interstitial cells of Cajal mediate mechanosensitive responses in the stomach

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

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