Sphingosine 1-phosphate induces contraction of coronary artery smooth muscle cells via S1P2

OBJECTIVES: Sphingosine 1-phosphate (Sph-1-P), a bioactive lipid derived from activated platelets, may play an important role in coronary artery spasm and hence the pathogenesis of ischemic heart diseases, since we reported that a decrease in coronary blood flow was induced by this lysophospholipid in an in vivo canine heart model [Cardiovasc. Res. 46 (2000) 119]. In this study, metabolism related to and cellular responses elicited by Sph-1-P were examined in human coronary artery smooth muscle cells (CASMCs). METHODS AND RESULTS: [3H]Sphingosine (Sph), incorporated into CASMCs, was converted to [3H]Sph-1-P intracellularly, but its stimulation-dependent formation and extracellular release were not observed. Furthermore, the cell surface Sph-1-P receptors of S1P family (previously called EDG) were found to be expressed in CASMCs. Accordingly, Sph-1-P seems to act as an extracellular mediator in CASMCs. Consistent with Sph-1-P-elicited coronary vasoconstriction in vivo, Sph-1-P strongly induced CASMC contraction, which was inhibited by JTE-013, a newly-developed specific antagonist of S1P(2) (EDG-5). Furthermore, C3 exoenzyme or Y-27632 inhibited the CASMC contraction induced by Sph-1-P, indicating Rho involvement. Finally, exogenously-added [3H]Sph-1-P underwent a rapid degradation. Since lipid phosphate phosphatases, ectoenzymes capable of dephosphorylating Sph-1-P, were expressed in CASMCs, Sph-1-P may be dephosphorylated by the ectophosphatases. CONCLUSIONS: Sph-1-P, derived from platelets and dephosphorylated on the cell surface, may induce the contraction of coronary artery smooth muscle cells through the S1P(2)/Rho signaling.     

Inhibitory effects of lysophosphatidic acid receptor-5 on cellular functions of sarcoma cells

Abstract

Lysophosphatidic acid (LPA) is a bioactive lipid that interacts with G protein-coupled LPA receptors (LPA receptor-1 (LPA₁) to LPA₆). Here, we investigated the effects of LPA signaling via LPA₅ on cellular functions of sarcoma cells by generating Lpar5 overexpressing and Lpar5 knockdown cells from rat osteosarcoma and malignant fibrous histiocytoma cells, respectively. The cell motility activity of Lpar5 overexpressing cells was significantly lower, while Lpar5 knockdown cells showed high cell motility, compared with respective controls. Gelatin zymography showed that LPA₅ suppressed the activation of matrix metalloproteinase-2. LPA₅ also inhibited the cell motility activity of endothelial cells, correlating with the expression levels of vascular endothelial growth factor genes. These results suggest that LPA signaling via LPA₅ negatively regulates the cellular functions of rat sarcoma cells.     

Sociocultural Beliefs,As Well As Goodness of Fit,Influence the Effectiveness of Coping in Japanese Workers

Background

Although the goodness-of-fit hypothesis (GOFH) is one of the most important theories in research about the effect of coping on distress related to different stressful situations, there has been a mixed response to it in the literature.

Purpose

The present study examined whether the effect of the sociocultural context in stressful situations is consistent with the GOFH. The study investigated sociocultural beliefs about the appropriateness of different coping strategies in a given group as the sociocultural context.

Method

Japanese employees (N?=?1,156) of an information technology company reported their appraisal of stressors’ controllability, the coping strategies they employed for the stressors, their sociocultural beliefs about coping strategies, and their psychological distress in response to the stressors.

Results

The GOFH was supported only for problem-focused coping with task stressors and not for interpersonal stressors. The applicability of the GOFH differed by sociocultural beliefs about coping, namely an appraisal of what coworkers might think about the appropriateness of the coping method.

Conclusion

These results suggest that it is important for managing stress to consider the sociocultural context as well as the GOFH.