Thromboxane A2 receptor-mediated G12/13-dependent glial morphological change

Honma, Shigeyoshi; Saika, Manami; Ohkubo, Satoko; Kurose, Hitoshi; Nakahata, Norimichi

doi:10.1016/j.ejphar.2006.06.062

Cited by 32 publications

(23 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These latter actions of Rho are mediated in part by the downstream Rho-dependent kinases I/II (ROCK1/2) coupled to myosin light chain (MLC) phosphorylation. Previous studies have indicated that PAR1 activation of 1321N1 cells triggers rapid ROCK-dependent changes in cell shape and organization of the actin cytoskeleton (29,36,42,56). However, treatment of 1321N1 cells with 10 M of the Y-27632 ROCK inhibitor for 1 h before thrombin stimulation did not attenuate the rate or peak magnitude of ATP release (Fig.…”

Section: Par1-activated Atp Release Is Suppressed By Bapta-buffering mentioning

confidence: 67%

See 1 more Smart Citation

Rho-family GTPases modulate Ca²⁺-dependent ATP release from astrocytes

Blum¹,

Joseph²,

Przybylski³

et al. 2008

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Blum AE, Joseph SM, Przybylski RJ, Dubyak GR. Rho-family GTPases modulate Ca 2ϩ -dependent ATP release from astrocytes. Am J Physiol Cell Physiol 295: C231-C241, 2008. First published May 21, 2008 doi:10.1152/ajpcell.00175.2008.-Previously, we reported that activation of G protein-coupled receptors (GPCR) in 1321N1 human astrocytoma cells elicits a rapid release of ATP that is partially dependent on a G q/phophospholipase C (PLC)/Ca 2ϩ mobilization signaling cascade. In this study we assessed the role of Rho-family GTPase signaling as an additional pathway for the regulation of ATP release in response to activation of protease-activated receptor-1 (PAR1), lysophosphatidic acid receptor (LPAR), and M3-muscarinic (M3R) GPCRs. Thrombin (or other PAR1 peptide agonists), LPA, and carbachol triggered quantitatively similar Ca 2ϩ mobilization responses, but only thrombin and LPA caused rapid accumulation of active GTP-bound Rho. The ability to elicit Rho activation correlated with the markedly higher efficacy of thrombin and LPA, relative to carbachol, as ATP secretagogues. Clostridium difficile toxin B and Clostridium botulinum C3 exoenzyme, which inhibit Rho-GTPases, attenuated the thrombin-and LPA-stimulated ATP release but did not decrease carbachol-stimulated release. Thus the ability of certain G q-coupled receptors to additionally stimulate Rho-GTPases acts to strongly potentiate a Ca 2ϩ -activated ATP release pathway. However, pharmacological inhibition of Rho kinase I/II or myosin light chain kinase did not attenuate ATP release. PAR1-induced ATP release was also reduced twofold by brefeldin treatment suggesting the possible mobilization of Golgi-derived, ATP-containing secretory vesicles. ATP release was also markedly repressed by the gap junction channel inhibitor carbenoxolone in the absence of any obvious thrombin-induced change in membrane permeability indicative of hemichannel gating. Rho GTPase; astrocyte; hemichannel EXTRACELLULAR NUCLEOTIDES act as autocrine/paracrine signaling molecules by targeting multiple P2 purinergic receptor subtypes that are differentially expressed in most tissues (7). Cells are able to tightly regulate the concentration of ATP and other nucleotides in the extracelluar space through a balance of release and extracellular metabolism of these nucleotides. The four sources of extracellular nucleotides are cell lysis, exocytosis, transport-mediated ATP release, and extracellular nucleotide kinases. In nonexcitable cells, such as astrocytes, unequivocal determination of ATP release mechanisms has remained elusive.In the brain, ATP can be released by astrocytes, or by other glial cell types, in response to diverse metabolic, mechanical, or inflammatory stimuli (8, 9). Extracellular ATP can target glia and neurons, as well as the smooth muscle cells and endothelial cells that populate cerebrovascular interfaces (1,21,32). Although purinergic signaling is an important element of the communication network between astrocytes and surrounding cells, the signaling events upstream of ATP ...

show abstract

Section: Par1-activated Atp Release Is Suppressed By Bapta-buffering mentioning

confidence: 67%

“…Previous studies have demonstrated that inhibition of either Rho-kinases by Y-27632 or myosin light chain kinase by ML-7 will suppress thrombin-stimulated rounding of 1321N1 cells, as well as remodeling of actin stress fibers (29,35,53). The inability of Y-27632 or ML-7 to attenuate ATP release (Fig.…”

Section: Discussionmentioning

confidence: 99%

Rho-family GTPases modulate Ca²⁺-dependent ATP release from astrocytes

Blum¹,

Joseph²,

Przybylski³

et al. 2008

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

“…Exoenzyme C3 from Clostridium botulinum, a cell-permeable Rho inhibitor, inhibits both astrocyte morphological changes (Höltje et al, 2005) and thrombininduced astrocyte proliferation (Citro et al, 2007). Moreover, Y27632 inhibits both morphological changes and proliferation induced by thromboxane A 2 receptor agonist in astrocytoma cells (Honma et al, 2006), suggesting that the morphological change is an initial phenomenon and a universal feature of proliferating astrocytes. Also, we might question how actin cytoskeletal rearrangement is affected by TRPC3-mediated Ca 2ϩ signaling.…”

Section: Par-1-induced Astrocytic Responsesmentioning

confidence: 99%

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.

View full text Add to dashboard Cite

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.

show abstract

“…Thus, RO-3244019 decreased bladder contraction frequency and increased the micturition threshold in isovolumetric bladder contraction and refill models, respectively (Cefalu et al, 2007), and improved intercontractile interval and voiding volumes as assessed by cystometry (Khera et al, 2007 (Hirata et al, 1991;Dorn and Becker, 1993;Kinsella et al, 1997;Offermanns, 2006;Nakahata 2008). Subsequent studies have strongly implicated G 12/13 -Rho as a major signaling pathway for TP receptors (Huang et al, 2004;Honma et al, 2006;Mir and Le Breton, 2008;Nakahata, 2008;Song et al, 2009;Zhang et al, 2009;Saito et al, 2010). More than any other prostanoid receptor, TP receptors have been subjected to extensive second messenger pathway analyses.…”

mentioning

confidence: 99%

“…Introduction of U-46619 into the fourth ventricle rapidly produces emesis (Kan et al, 2008). In relation to the CNS, TP receptors are reported to be expressed on oligodendrocytes (Blackman et al, 1998;Mir and Le Breton, 2008) and human astrocytoma cells (Honma et al, 2006).…”

mentioning

confidence: 99%