| 22359668 | In this study, we investigated the effect of lysophosphatidic acid (LPA), a ubiquitous metabolite in membrane phospholipid synthesis, on the senescence program of human MSCs |
| 22359668 | We show that MSCs preferentially express the LPA receptor subtype 1, and an abrogation of the receptor engagement with the antagonistic compound Ki16425 attenuates senescence induction in continually propagated human MSCs |
| 22359668 | Expressions of p16(Ink4a), Rb, p53, and p21(Cip1), which have been associated with cellular senescence, were all reduced in human MSCs by the pharmacological inhibition of LPA signaling |
| 22359668 | Prevention of LPA receptor engagement also promoted ubiquitination-mediated c-Myc elimination in MSCs, and consequently the entry into a quiescent state, G(0) phase, of the cell cycle |
| 22359668 | Collectively, these results highlight the potential of pharmacological intervention against LPA signaling for blunting senescence-associated loss of function characteristic of human MSCs |
| 20457578 | We previously showed that lysophosphatidic acid (LPA) and an adenylyl cyclase inhibitor (ACI) stimulate mitogenic activation of senescent human diploid fibroblasts |
| 20457578 | Because the modulation of cell proliferation may affect wound healing in aged organisms, we studied the effects of LPA and ACI on in vivo skin wound healing in aged Fisher 344 rats |
| 20457578 | We found that, in aged rats, wound healing improved in animals treated with LPA and/or ACI (relative to untreated controls), as assessed by histological analysis of reepithelialization and immunostaining for proliferating cell nuclear antigen |
| 20457578 | The age-dependent activation of mitogenic responses by LPA and ACI was confirmed in other cell types |
| 20457578 | Taken together, our findings suggest that the activation of mitogenic potential in senescent cells by LPA and/or ACI may translate into enhanced in vivo wound healing and tissue regeneration in aged animals |
| 19563823 | The expression of some genes, including EGR 1/3 and MRRF, was controlled by LPA similarly in young and senescent cells, showing a typical time-dependent up-and-down expression profile |
| 19563823 | In contrast, some other genes, including DUSP6, CYR61, and F3, showed sustained upregulation in senescent HDFs later after LPA treatment |
| 19563823 | These genes might be involved in altered LPA responsiveness during the aging process |
| 18729810 | This study was designed to elucidate the molecular mechanism underlying lysophosphatidic acid (LPA) and adenylyl cyclase inhibitor SQ22536 (ACI)-induced senescent human diploid fibroblast (HDF) proliferation |
| 18729810 | LPA increased p-Ser485/491-AMPKalpha, presumably by activating cAMP-dependent protein kinase (PKA) |
| 18729810 | Our data demonstrated that both LPA and ACI inhibit the catalytic activity of AMPKalpha and p53 by differentially regulating phosphorylation of AMPKalpha, causing increased senescent cell proliferation |
| 17081159 | When the expression of Gravin and AKAP79 was blocked by small interference RNA transfection, the basal level of cAMP was greatly reduced and the cAMP status after LPA treatment was also reversed |
| 17081159 | This study also demonstrates that Gravin is especially important for the long-term activation of PKC by LPA in senescent cells |
| 16672767 | Lysophosphatidic acid (LPA) is a phospholipid growth factor that acts through G-protein-coupled receptors |
| 16672767 | Senescence-associated increase of cAMP after LPA treatment correlated well with increased CREB phosphorylation accompanying activation of PKA in senescent cells |
| 16672767 | In senescent cells, after LPA treatment, the expression of c-fos and COX-2 decreased initially, followed by an increase |
| 16672767 | In young HDFs, CREB phosphorylation decreased following LPA treatment, and both c-fos and COX-2 protein levels increased rapidly |
| 16516270 | This study attempts to elucidate the molecular mechanisms underlying the ageing-dependent cAMP profiles in human diploid fibroblasts stimulated by lysophosphatidic acid (LPA) |
| 16516270 | In young cells, when Gialpha activity was inhibited by pertussis toxin pretreatment, or when its expression was blocked by siRNA, the pattern of changes in cAMP levels in response to LPA was similar to that seen in senescent cells |
| 16516270 | In senescent cells treated with PKC-specific inhibitors, bis-indolylmaleimide, Go6976, rottlerin, and PKCvarepsilonV1, LPA-induced cAMP accumulation was inhibited, indicating that increased ACs in response to LPA occur via the activation of protein kinase Cs |
| 16516270 | These results suggest that the senescence-associated increase of cAMP levels after LPA treatment is associated with reduced Gialpha, increased AC II, IV, and VI proteins, and PKC-dependent stimulation of their activities and provide an explanation for the age-dependent differences in cAMP-related physiological responses |
| 12646237 | Lysophosphatidic acid (LPA) is a lipid mitogen that acts through G-protein-coupled receptors |
| 12646237 | LPA responsiveness has been reported to be dependent on the senescent state of the cells |
| 12646237 | Decreased Gis and Gi-coupled LPA receptors may reduce the inhibitory effect of Gi alpha on adenylyl cyclases (ACs), resulting in cAMP accumulation via activation of adenylyl cyclase in senescent fibroblasts |
| 12086695 | Changes in the signal transduction efficiency of senescent cells led us to compare the signaling events induced by two mitogenic agonists, platelet-derived growth factor (PDGF) and lysophosphatidic acid (LPA) in presenescent and senescent or near-senescent human diploid fibroblasts |
| 12086695 | When the changes in intracellular [Ca(2+)](i) were analyzed, both PDGF and LPA generated a rhythmic increase in [Ca(2+)](i) in presenescent cells |
| 12086695 | LPA resulted in a 2-3-fold increase in thymidine incorporation even in the near-senescent cells |
| 8866734 | In comparison with the young En(a-) red blood cell membranes, the number and the distribution density of lectin receptor sites on the old ones for Limulus polyphemus (LPA), Canavalia ensiformis (Con A), Triticum vulgaris (WGA) and Bauhinia purpurea (BPA) were significantly lower |
| 8866734 | It is thought that En(a-) red blood cell ageing is accompanied by elimination of some sialoglycoconjugates which have affinity for LPA, Con A, WGA and BPA, whereas En(a-) red blood cells lack glycophorin A |
