{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T11:03:16Z","timestamp":1784372596651,"version":"3.55.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Palmitoylation, the reversible addition of the lipid palmitate to a cysteine, can alter protein localization, stability, and function. The ZDHHC family of protein acyl transferases catalyzes palmitoylation of numerous proteins. The role of ZDHHC enzymes in intact tissue and in vivo is largely unknown. Herein, we characterize vascular functions in a mouse that expresses a nonfunctional ZDHHC21 (F233\u0394).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>Physiological studies of isolated aortae and mesenteric arteries from F233\u0394 mice revealed an unexpected defect in responsiveness to phenylephrine, an \u03b11 adrenergic receptor agonist. In vivo, F233\u0394 mice displayed a blunted response to infusion of phenylephrine, and they were found to have elevated catecholamine levels and elevated vascular \u03b11 adrenergic receptor gene expression. Telemetry studies showed that the F233\u0394 mice were tachycardic and hypotensive at baseline, consistent with diminished vascular tone. In biochemical studies, ZDHHC21 was shown to palmitoylate the \u03b11D adrenoceptor and to interact with it in a molecular complex, thus suggesting a possible molecular mechanism by which the receptor can be regulated by ZDHHC21.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Together, the data support a model in which ZDHHC21 F233\u0394 diminishes the function of vascular \u03b11 adrenergic receptors, leading to reduced vascular tone, which manifests in vivo as hypotension and tachycardia. This is to our knowledge the first demonstration of a ZDHHC isoform affecting vascular function in vivo and identifies a novel molecular mode of regulation of vascular tone and blood pressure.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.115.306942","type":"journal-article","created":{"date-parts":[[2015,12,30]],"date-time":"2015-12-30T03:13:26Z","timestamp":1451445206000},"page":"370-379","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["The Protein Acyl Transferase ZDHHC21 Modulates \u03b11 Adrenergic Receptor Function and Regulates Hemodynamics"],"prefix":"10.1161","volume":"36","author":[{"given":"Ethan P.","family":"Marin","sequence":"first","affiliation":[{"name":"From the Section of Nephrology (E.P.M., L.J., J.M., H.V.) and Department of Dermatology (L.M.M.), Yale School of Medicine, New Haven, CT; and Vascular Biology and Therapeutics Program, Department of Pharmacology, Yale University School of Medicine, New Haven, CT (A.D.L., K.F.H., A.K.L., W.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levente","family":"Jozsef","sequence":"additional","affiliation":[{"name":"From the Section of Nephrology (E.P.M., L.J., J.M., H.V.) and Department of Dermatology (L.M.M.), Yale School of Medicine, New Haven, CT; and Vascular Biology and Therapeutics Program, Department of Pharmacology, Yale University School of Medicine, New Haven, CT (A.D.L., K.F.H., A.K.L., W.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annarita","family":"Di Lorenzo","sequence":"additional","affiliation":[{"name":"From the Section of Nephrology (E.P.M., L.J., J.M., H.V.) and Department of Dermatology (L.M.M.), Yale School of Medicine, New Haven, CT; and Vascular Biology and Therapeutics Program, Department of Pharmacology, Yale University School of Medicine, New Haven, CT (A.D.L., K.F.H., A.K.L., W.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara F.","family":"Held","sequence":"additional","affiliation":[{"name":"From the Section of Nephrology (E.P.M., L.J., J.M., H.V.) and Department of Dermatology (L.M.M.), Yale School of Medicine, New Haven, CT; and Vascular Biology and Therapeutics Program, Department of Pharmacology, Yale University School of Medicine, New Haven, CT (A.D.L., K.F.H., A.K.L., W.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia K.","family":"Luciano","sequence":"additional","affiliation":[{"name":"From the Section of Nephrology (E.P.M., L.J., J.M., H.V.) and Department of Dermatology (L.M.M.), Yale School of Medicine, New Haven, CT; and Vascular Biology and Therapeutics Program, Department of Pharmacology, Yale University School of Medicine, New Haven, CT (A.D.L., K.F.H., A.K.L., W.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Melendez","sequence":"additional","affiliation":[{"name":"From the Section of Nephrology (E.P.M., L.J., J.M., H.V.) and Department of Dermatology (L.M.M.), Yale School of Medicine, New Haven, CT; and Vascular Biology and Therapeutics Program, Department of Pharmacology, Yale University School of Medicine, New Haven, CT (A.D.L., K.F.H., A.K.L., W.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard M.","family":"Milstone","sequence":"additional","affiliation":[{"name":"From the Section of Nephrology (E.P.M., L.J., J.M., H.V.) and Department of Dermatology (L.M.M.), Yale School of Medicine, New Haven, CT; and Vascular Biology and Therapeutics Program, Department of Pharmacology, Yale University School of Medicine, New Haven, CT (A.D.L., K.F.H., A.K.L., W.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heino","family":"Velazquez","sequence":"additional","affiliation":[{"name":"From the Section of Nephrology (E.P.M., L.J., J.M., H.V.) and Department of Dermatology (L.M.M.), Yale School of Medicine, New Haven, CT; and Vascular Biology and Therapeutics Program, Department of Pharmacology, Yale University School of Medicine, New Haven, CT (A.D.L., K.F.H., A.K.L., W.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Sessa","sequence":"additional","affiliation":[{"name":"From the Section of Nephrology (E.P.M., L.J., J.M., H.V.) and Department of Dermatology (L.M.M.), Yale School of Medicine, New Haven, CT; and Vascular Biology and Therapeutics Program, Department of Pharmacology, Yale University School of Medicine, New Haven, CT (A.D.L., K.F.H., A.K.L., W.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-6175.2005.05300.x"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2084"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.269514"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.03.042"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07605"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1293"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00989"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.079426"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr308"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds441"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2011.11.002"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2015.06.004"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.4339"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2006.03.010"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200601051"},{"key":"e_1_3_5_17_2","first-page":"1","article-title":"Dhhc-7 and 21 are palmitoylacyltransferases for sex steroid receptors.","author":"Pedram A","year":"2011","unstructured":"Pedram A, Razandi M, Deschenes RJ, Levin ER. Dhhc-7 and 21 are palmitoylacyltransferases for sex steroid receptors. Mol. Biol. Cell. 2011:1\u201339.","journal-title":"Mol. Biol. Cell"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000748"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01144-08"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/84.1.59"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01000.2007"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1677\/JME-08-0114"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103816200"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2005.10.004"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2006.05.015"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI14001"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.237594"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.302.1.58"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(95)00026-1"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.D011106"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.4161\/adip.22117"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.11.027"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-008-0368-6"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.104.007500"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2003.11.014"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.0000022062.70639.1c"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.05.011"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2063193"},{"key":"e_1_3_5_39_2","first-page":"1","volume-title":"Neural Control of Renal Function. Colloquium Series on Integrated Systems Physiology: From Molecule to Function","author":"Kopp UC","year":"2011","unstructured":"Kopp UC. Neural Control of Renal Function. Colloquium Series on Integrated Systems Physiology: From Molecule to Function. San Rafael, CA: Morgan & Claypool Life Sciences; 2011:1\u201396."},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00462.x"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.2174\/138161206776873716"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.189977"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.306183"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2013.09.018"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2014.01.008"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2011.07.028"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1222384110"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000985"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092194"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/377239a0"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2006.04.013"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M800270-JLR200"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1769"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.362"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.115.306942","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:10:14Z","timestamp":1715555414000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.115.306942"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2]]},"references-count":53,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,2]]}},"alternative-id":["10.1161\/ATVBAHA.115.306942"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.115.306942","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2]]},"assertion":[{"value":"2015-11-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-12-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-12-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}