{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:45:05Z","timestamp":1791121505989,"version":"4.1.0"},"reference-count":57,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,12,1]]},"abstract":"<jats:p>Uterine leiomyomas, or fibroids, are the most common tumors of the myometrium. The ELT3 cell line, derived from Eker rat leiomyoma, has been successfully used as a model for the study of leiomyomas. We have demonstrated previously the potent mitogenic properties of the peptidic hormone endothelin (ET)-1 in this cell line. Here we investigated the antiapoptotic effect of ET-1 in ELT3 cells. We found that 1) serum starvation of ELT3 cells induced an apoptotic process characterized by cytochrome c release from mitochondria, caspase-3\/7 activation, nuclei condensation and DNA fragmentation; 2) ET-1 prevented the apoptotic process; and 3) this effect of ET-1 was fully reproduced by ETB agonists. In contrast, no antiapoptotic effect of ET-1 was observed in normal myometrial cells. A pharmacological approach showed that the effect of ET-1 on caspase-3\/7 activation in ELT3 cells was not dependent on phosphatidylinositol 3-kinase, ERK1\/2, or phospholipase D activities. However, inhibitors of sphingosine kinase-1 (SphK1), dimethylsphingosine and threo-dihydrosphingosine, reduced the effect of ET-1 by about 50%. Identical results were obtained when SphK1 expression was down-regulated in ELT3 cells transfected with SphK1 small interfering RNA. Furthermore, serum starvation induced a decrease in SphK1 activity that was prevented by ET-1 without affecting the level of SphK1 protein expression. Finally, sphingosine 1-phosphate, the product of SphK activity, was as efficient as ET-1 in inhibiting serum starvation-induced caspase-3\/7 activation. Together, these results demonstrate that ET-1 possesses a potent antiapoptotic effect in ELT3 cells that involves sphingolipid metabolism through the activation of SphK1.<\/jats:p>","DOI":"10.1210\/en.2006-0291","type":"journal-article","created":{"date-parts":[[2006,9,8]],"date-time":"2006-09-08T00:30:16Z","timestamp":1157675416000},"page":"5873-5882","source":"Crossref","is-referenced-by-count":33,"title":["Endothelin-1 Inhibits Apoptosis through a Sphingosine Kinase 1-Dependent Mechanism in Uterine Leiomyoma ELT3 Cells"],"prefix":"10.1210","volume":"147","author":[{"given":"Marie-Noe\u0308lle","family":"Raymond","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Bole-Feysot","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Banno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Tanfin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Robin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071612490312700_R1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1093\/ajcp\/94.4.435","article-title":"The frequency of uterine leiomyomas","volume":"94","author":"Cramer","year":"1990","journal-title":"Am J Clin Pathol"},{"key":"2020071612490312700_R2","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1126\/science.1112063","article-title":"Uterine fibroids: the elephant in the room","volume":"308","author":"Walker","year":"2005","journal-title":"Science"},{"issue":"Suppl 5","key":"2020071612490312700_R3","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1289\/ehp.00108s5817","article-title":"Pregnancy, parturition, and prostaglandins: defining uterine leiomyomas","volume":"108","author":"Cesen-Cummings","year":"2000","journal-title":"Environ Health Perspect"},{"issue":"Pt 1","key":"2020071612490312700_R4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj3260001","article-title":"Caspases: the executioners of apoptosis","volume":"326","author":"Cohen","year":"1997","journal-title":"Biochem J"},{"key":"2020071612490312700_R5","first-page":"1568","article-title":"Rodent model of reproductive tract leiomyomata. 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