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To examine the role of the cAMP pathway in cholesterol accumulation, we treated two CF model cell lines with the Rp diastereomer of adenosine 3\u2032,5\u2032-cyclic monophosphorothioate ( Rp-cAMPS) and visualized by filipin staining. Rp-cAMPS treatment eliminated cholesterol accumulation in CF cells, whereas 8-bromo-cAMP treatment led to cholesterol accumulation in wild-type cells. To confirm these findings in an independent model system, we also examined the role of cAMP in modulating cholesterol accumulation in Niemann-Pick type C (NPC) fibroblasts. Expression of the protein related to NPC, NPC1, is also directly regulated by cAMP; therefore, it is postulated that NPC cells exhibit the same cAMP-mediated control of cholesterol accumulation. Cholesterol accumulation in NPC cells also was reduced by the presence of Rp-cAMPS. Expression of \u03b2-arrestin-2 (\u03b2arr2), a marker of cellular response to cAMP signaling, was significantly elevated in CF model cells, Cftr<jats:sup>\u2212\/\u2212<\/jats:sup>MNE, primary tissue obtained by nasal scrapes from CF subjects, and in NPC fibroblasts compared with respective controls.<\/jats:p>","DOI":"10.1152\/ajplung.90402.2008","type":"journal-article","created":{"date-parts":[[2008,9,13]],"date-time":"2008-09-13T00:44:34Z","timestamp":1221266674000},"page":"L809-L819","source":"Crossref","is-referenced-by-count":34,"title":["cAMP-mediated regulation of cholesterol accumulation in cystic fibrosis and Niemann-Pick type C cells"],"prefix":"10.1152","volume":"295","author":[{"given":"Mary E.","family":"Manson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah A.","family":"Corey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole M.","family":"White","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Kelley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.156.4.96-11058"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.20294"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407521200"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200207-765OC"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2007.08.013"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2865"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-001-0436-8"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1995.269.5.L625"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(98)00107-6"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03350"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1210\/me.2002-0093"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1002\/path.2118"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119828"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00231.2007"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2357"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9560"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2004.15.1255"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00127.2003"},{"key":"R19","doi-asserted-by":"crossref","unstructured":"Kruth HS, Comly ME, Butler JD, Vanier MT, Fink JK, Wenger DA, Patel S, Pentchev PG.Type C Niemann-Pick disease. 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