title: Albumin-induced apoptosis of tubular cells is modulated by BASP1.
abstract: Albuminuria promotes tubular injury and cell death, and is associated with faster progression of chronic kidney disease (CKD) to end-stage renal disease. However, the molecular mechanisms regulating tubular cell death in response to albuminuria are not fully understood. Brain abundant signal protein 1 (BASP1) was recently shown to mediate glucose-induced apoptosis in tubular cells. We have studied the role of BASP1 in albumin-induced tubular cell death. BASP1 expression was studied in experimental puromycin aminonucleoside-induced nephrotic syndrome in rats and in human nephrotic syndrome. The role of BASP1 in albumin-induced apoptosis was studied in cultured human HK2 proximal tubular epithelial cells. Puromycin aminonucleoside induced proteinuria and increased total kidney BASP1 mRNA and protein expression. Immunohistochemistry localized the increased BASP1 to tubular cells. BASP1 expression colocalized with deoxynucleotidyl-transferase-mediated dUTP nick-end labeling staining for apoptotic cells. Increased tubular BASP1 expression was observed in human proteinuric nephropathy by immunohistochemistry, providing evidence for potential clinical relevance. In cultured tubular cells, albumin induced apoptosis and increased BASP1 mRNA and protein expression at 6-48 h. Confocal microscopy localized the increased BASP1 expression in albumin-treated cells mainly to the perinuclear area. A peripheral location near the cell membrane was more conspicuous in albumin-treated apoptotic cells, where it colocalized with actin. Inhibition of BASP1 expression by a BASP1 siRNA protected from albumin-induced apoptosis. In conclusion, albumin-induced apoptosis in tubular cells is BASP1-dependent. This information may be used to design novel therapeutic approaches to slow CKD progression based on protection of tubular cells from the adverse consequences of albuminuria.
authors: 1] Instituto de Investigacion Sanitaria IDIPAZ, Madrid, Spain [2] REDINREN, Madrid, Spain.
authors: M D
authors: MD
authors: Sanchez-Niño
authors: 1] REDINREN, Madrid, Spain [2] IIS-Fundación Jiménez Díaz-Universidad Autónoma de Madrid and Fundación Renal Iñigo Alvarez de Toledo-IRSIN, Madrid, Spain.
authors: B
authors: B
authors: Fernandez-Fernandez
authors: 1] REDINREN, Madrid, Spain [2] IIS-Fundación Jiménez Díaz-Universidad Autónoma de Madrid and Fundación Renal Iñigo Alvarez de Toledo-IRSIN, Madrid, Spain.
authors: M V
authors: MV
authors: Perez-Gomez
authors: 1] REDINREN, Madrid, Spain [2] IIS-Fundación Jiménez Díaz-Universidad Autónoma de Madrid and Fundación Renal Iñigo Alvarez de Toledo-IRSIN, Madrid, Spain.
authors: J
authors: J
authors: Poveda
authors: 1] REDINREN, Madrid, Spain [2] IIS-Fundación Jiménez Díaz-Universidad Autónoma de Madrid and Fundación Renal Iñigo Alvarez de Toledo-IRSIN, Madrid, Spain.
authors: A B
authors: AB
authors: Sanz
authors: 1] REDINREN, Madrid, Spain [2] IIS-Fundación Jiménez Díaz-Universidad Autónoma de Madrid and Fundación Renal Iñigo Alvarez de Toledo-IRSIN, Madrid, Spain.
authors: P
authors: P
authors: Cannata-Ortiz
authors: 1] REDINREN, Madrid, Spain [2] IIS-Fundación Jiménez Díaz-Universidad Autónoma de Madrid and Fundación Renal Iñigo Alvarez de Toledo-IRSIN, Madrid, Spain.
authors: M
authors: M
authors: Ruiz-Ortega
authors: IIS-Fundación Jiménez Díaz-Universidad Autónoma de Madrid and Fundación Renal Iñigo Alvarez de Toledo-IRSIN, Madrid, Spain.
authors: J
authors: J
authors: Egido
authors: 1] Instituto de Investigacion Sanitaria IDIPAZ, Madrid, Spain [2] REDINREN, Madrid, Spain.
authors: R
authors: R
authors: Selgas
authors: 1] REDINREN, Madrid, Spain [2] IIS-Fundación Jiménez Díaz-Universidad Autónoma de Madrid and Fundación Renal Iñigo Alvarez de Toledo-IRSIN, Madrid, Spain.
authors: A
authors: A
authors: Ortiz
mesh_terms: D000418:Albumins / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000418:Albumins; C104089:BASP1 protein, human; D002148:Calmodulin-Binding Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C066853:Basp1 protein, rat