{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:57:47Z","timestamp":1761526667635,"version":"build-2065373602"},"reference-count":75,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CNPq, CAPES, and FAPERJ"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ceramide kinase (CerK) catalyzes the phosphorylation of ceramide to ceramide-1-phosphate (C1P), a bioactive sphingolipid with diverse signaling roles. While CerK has been identified in several cellular compartments, its presence and functional significance in kidney proximal tubules remain unexplored. Herein, we report the first characterization of CerK activity in basolateral membranes (BLMs) from porcine proximal tubule cells. We demonstrate that BLM fractions contain neutral and acidic sphingomyelinases, providing local substrate for CerK, which efficiently generates C1P under physiological pH (6.5\u20137.2) and temperature (30\u201337 \u00b0C) conditions. Enzyme activity was stimulated by cAMP in a protein kinase A-dependent manner but was not affected by angiotensin II. Lipidomic analysis confirmed the presence of C1P in human proximal tubule (HK-2) cells under basal conditions and revealed changes during ischemic stress. Transcriptomic analysis of kidney biopsies from patients with chronic kidney disease (CKD) further uncovered coordinated remodeling of sphingolipid metabolism genes, with increased expression of ceramidases (ASAH1 and NAAA) and downregulation of ceramide synthases (CERS4, CERS5), consistent with adaptive regulation of the Cer\/CerK\/C1P axis. Together, these findings identify for the very first time CerK activity in renal BLM, establish its biochemical requirements, and highlight its potential role in modulating transporter function and sphingolipid signaling in physiology and kidney disease.<\/jats:p>","DOI":"10.3390\/ijms262110373","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:51:42Z","timestamp":1761526302000},"page":"10373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of Ceramide Kinase from Basolateral Membranes of Kidney Proximal Tubules: Kinetics, Physicochemical Requirements, and Physiological Relevance"],"prefix":"10.3390","volume":"26","author":[{"given":"Gloria M. R. S.","family":"Grelle","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Biomembranas, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Ilha do Fund\u00e3o, Rio de Janeiro 21941-902, Brazil"},{"name":"Laborat\u00f3rio de Metabol\u00f4mica, LADETEC, Instituto de Qu\u00edmica, Universidade Federal do Rio de Janeiro, Ilha do Fund\u00e3o, Rio de Janeiro 21941-598, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsey M. P.","family":"Cabral","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biomembranas, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Ilha do Fund\u00e3o, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando G.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biomembranas, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Ilha do Fund\u00e3o, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9312-3442","authenticated-orcid":false,"given":"Giovane G.","family":"Tortelote","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, Tulane University, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Garrett","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Metabol\u00f4mica, LADETEC, Instituto de Qu\u00edmica, Universidade Federal do Rio de Janeiro, Ilha do Fund\u00e3o, Rio de Janeiro 21941-598, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8009-7273","authenticated-orcid":false,"given":"Adalberto","family":"Vieyra","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de F\u00edsico-Qu\u00edmica Biol\u00f3gica A\u00edda Hasson Voloch, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Ilha do Fund\u00e3o, Rio de Janeiro 21941-902, Brazil"},{"name":"Centro Nacional de Biologia Estrutural e Bioimagem\u2014CENABIO, Universidade Federal do Rio de Janeiro, Ilha do Fund\u00e3o, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1244-814X","authenticated-orcid":false,"given":"Rafael H. F.","family":"Valverde","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biomembranas, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Ilha do Fund\u00e3o, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2415-7753","authenticated-orcid":false,"given":"Celso","family":"Caruso-Neves","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Sinaliza\u00e7\u00e3o Celular, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Ilha do Fund\u00e3o, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7155-1174","authenticated-orcid":false,"given":"Marcelo","family":"Einicker-Lamas","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biomembranas, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Ilha do Fund\u00e3o, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0005-2736(00)00219-4","article-title":"Angiotensin-(1-7) modulates the ouabain-insensitive Na+-ATPase activity from basolateral membrane of the proximal tubule","volume":"1467","author":"Lara","year":"2000","journal-title":"Biochim. 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