title: Cyclic adenosine monophosphate protects renal cell lines against amphotericin B toxicity in a PKA-independent manner.
abstract: Amphotericin B is the "gold standard" agent in the management of serious systemic fungal infections. However, this drug can cause nephrotoxicity, which contributes up to 25% of all acute kidney injuries in critically ill patients. Cyclic adenosine monophosphate can protect kidney cells from death due to injury or drug exposure in some cases. Hence, the objective of this work was to evaluate if cAMP could prevent cell death that occurs in renal cell lines subjected to AmB treatment and, if so, to assess the involvement of PKA in the transduction of this signal. Two different renal cell lines (LLC-PK1 and MDCK) were used in this study. MTT and flow cytometry assays showed increased cell survival when cells were exposed to cAMP in a PKA-independent manner, which was confirmed by western blot. This finding suggests that cAMP (db-cAMP) may prevent cell death caused by exposure to AmB. This is the first time this effect has been identified when renal cells are exposed to AmB's nephrotoxic potential.
authors.affiliation: a Departamento de Bioquímica e Imunologia , Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte , MG , Brazil .
authors.forename: A F
authors.initials: AF
authors.lastname: Ferreira
authors.affiliation: a Departamento de Bioquímica e Imunologia , Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte , MG , Brazil .
authors.forename: F D
authors.initials: FD
authors.lastname: França
authors.affiliation: b Departamento de Ciências Biológicas , Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto , Mouro Preto , MG , Brazil .
authors.forename: J V
authors.initials: JV
authors.lastname: Rossoni
authors.affiliation: a Departamento de Bioquímica e Imunologia , Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte , MG , Brazil .
authors.forename: P H L
authors.initials: PH
authors.lastname: Viana
authors.affiliation: c Departamento de Biologia , Universidade Estadual Paulista "Júlio de Mesquita Filho", Instituto de Biociências , Rio Claro , SP , Brazil , and.
authors.forename: K C M
authors.initials: KC
authors.lastname: Moraes
authors.affiliation: a Departamento de Bioquímica e Imunologia , Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte , MG , Brazil .
authors.forename: D A
authors.initials: DA
authors.lastname: Gomes
authors.affiliation: b Departamento de Ciências Biológicas , Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto , Mouro Preto , MG , Brazil .
authors.forename: D C
authors.initials: DC
authors.lastname: Costa
authors.affiliation: d Departamento de Análises Clinicas e Toxicológicas , Faculdade de Farmácia, Universidade Federal de Minas Gerais , Bioquímica, Belo Horizonte , Brazil.
authors.forename: C A
authors.initials: CA
authors.lastname: Tagliati
authors.affiliation: a Departamento de Bioquímica e Imunologia , Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte , MG , Brazil .
authors.forename: M M
authors.initials: MM
authors.lastname: Chaves
mesh_terms: D000666:Amphotericin B / Q000633:toxicity*; D000818:Animals; D000935:Antifungal Agents / Q000633:toxicity*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000008:administration & dosage* / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004285:Dogs; D005434:Flow Cytometry; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D018374:LLC-PK1 Cells; D061985:Madin Darby Canine Kidney Cells; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: cAMP; cell protection; nephrotoxicity