Your browser doesn't support javascript.
loading
Arginine reprogramming in ADPKD results in arginine-dependent cystogenesis.
Trott, Josephine F; Hwang, Vicki J; Ishimaru, Tatsuto; Chmiel, Kenneth J; Zhou, Julie X; Shim, Kyuhwan; Stewart, Benjamin J; Mahjoub, Moe R; Jen, Kuang-Yu; Barupal, Dinesh K; Li, Xiaogang; Weiss, Robert H.
Afiliación
  • Trott JF; Division of Nephrology, Department of Internal Medicine, University of California , Davis, California.
  • Hwang VJ; Division of Nephrology, Department of Internal Medicine, University of California , Davis, California.
  • Ishimaru T; Division of Nephrology, Department of Internal Medicine, University of California , Davis, California.
  • Chmiel KJ; Division of Nephrology, Department of Internal Medicine, University of California , Davis, California.
  • Zhou JX; Kidney Institute, Department of Internal Medicine, University of Kansas Medical Center , Kansas City, Kansas.
  • Shim K; Division of Nephrology, Department of Medicine, Washington University , St. Louis, Missouri.
  • Stewart BJ; Lawrence Livermore National Laboratory , Livermore, California.
  • Mahjoub MR; Division of Nephrology, Department of Medicine, Washington University , St. Louis, Missouri.
  • Jen KY; Department of Pathology, University of California , Davis, California.
  • Barupal DK; West Coast Metabolomics Center, University of California , Davis, California.
  • Li X; Kidney Institute, Department of Internal Medicine, University of Kansas Medical Center , Kansas City, Kansas.
  • Weiss RH; Division of Nephrology, Department of Internal Medicine, University of California , Davis, California.
Am J Physiol Renal Physiol ; 315(6): F1855-F1868, 2018 12 01.
Article en En | MEDLINE | ID: mdl-30280600
Research into metabolic reprogramming in cancer has become commonplace, yet this area of research has only recently come of age in nephrology. In light of the parallels between cancer and autosomal dominant polycystic kidney disease (ADPKD), the latter is currently being studied as a metabolic disease. In clear cell renal cell carcinoma (RCC), which is now considered a metabolic disease, we and others have shown derangements in the enzyme arginosuccinate synthase 1 (ASS1), resulting in RCC cells becoming auxotrophic for arginine and leading to a new therapeutic paradigm involving reducing extracellular arginine. Based on our earlier finding that glutamine pathways are reprogrammed in ARPKD, and given the connection between arginine and glutamine synthetic pathways via citrulline, we investigated the possibility of arginine reprogramming in ADPKD. We now show that, in a remarkable parallel to RCC, ASS1 expression is reduced in murine and human ADPKD, and arginine depletion results in a dose-dependent compensatory increase in ASS1 levels as well as decreased cystogenesis in vitro and ex vivo with minimal toxicity to normal cells. Nontargeted metabolomics analysis of mouse kidney cell lines grown in arginine-deficient versus arginine-replete media suggests arginine-dependent alterations in the glutamine and proline pathways. Thus, depletion of this conditionally essential amino acid by dietary or pharmacological means, such as with arginine-degrading enzymes, may be a novel treatment for this disease.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arginina / Riñón Poliquístico Autosómico Dominante / Proliferación Celular / Metabolismo Energético / Riñón Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Am J Physiol Renal Physiol Asunto de la revista: FISIOLOGIA / NEFROLOGIA Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arginina / Riñón Poliquístico Autosómico Dominante / Proliferación Celular / Metabolismo Energético / Riñón Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Am J Physiol Renal Physiol Asunto de la revista: FISIOLOGIA / NEFROLOGIA Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos