TY - JOUR
T1 - The nephroprotection exerted by curcumin in maleate-induced renal damage is associated with decreased mitochondrial fission and autophagy
AU - Molina-Jijón, Eduardo
AU - Aparicio-Trejo, Omar Emiliano
AU - Rodríguez-Muñoz, Rafael
AU - León-Contreras, Juan Carlos
AU - del Carmen Cárdenas-Aguayo, María
AU - Medina-Campos, Omar Noel
AU - Tapia, Edilia
AU - Sánchez-Lozada, Laura Gabriela
AU - Hernández-Pando, Rogelio
AU - Reyes, José L.
AU - Arreola-Mendoza, Laura
AU - Pedraza-Chaverri, José
N1 - Publisher Copyright:
© 2016 International Union of Biochemistry and Molecular Biology
PY - 2016/11/1
Y1 - 2016/11/1
N2 - We have previously reported that the antioxidant curcumin exerts nephroprotection in maleate-induced renal damage, a model associated with oxidative stress. However, the mechanisms involved in curcumin protective effect were not explored, to assess this issue, curcumin was administered daily by gavage (150 mg/kg) five days before a single maleate (400 mg/kg)-injection. Curcumin prevented maleate-induced proteinuria, increased heat shock protein of 72 KDa (Hsp72) expression, and decreased plasma glutathione peroxidase activity. Maleate-induced oxidative stress by increasing the nicotinamide–adenine dinucleotide phosphate oxidase 4 (NOX4) and mitochondrial complex I-dependent superoxide anion (O2•—) production, formation of malondialdehyde (MDA)- and 3-nitrotyrosine (3-NT)-protein adducts and protein carbonylation and decreased GSH/GSSG ratio. Curcumin treatment ameliorated all the above-described changes. The maleate-induced epithelial damage, evaluated by claudin-2 and occludin expressions, was ameliorated by curcumin. It was found that maleate-induced oxidative stress promoted mitochondrial fission, evaluated by dynamin-related protein (Drp) 1 and fission (Fis) 1 expressions and by electron-microscopy, and autophagy, evaluated by phospho-threonine 389 from p70 ribosomal protein S6 kinase (p-Thr 389 p70S6K), beclin 1, microtubule-associated protein 1A/1B-light chain 3 phosphatidylethanolamine conjugate (LC3-II), autophagy-related gene 5 and 12 (Atg5-Atg12) complex, p62, and lysosomal-associated membrane protein (LAMP)-2 expressions in isolated proximal tubules and by electron-microscopy and LC-3 immunolabelling. Curcumin treatment ameliorated these changes. Moreover, curcumin alone induced autophagy in proximal tubules. These data suggest that the nephroprotective effect exerted by curcumin in maleate-induced renal damage is associated with decreased mitochondrial fission and autophagy.
AB - We have previously reported that the antioxidant curcumin exerts nephroprotection in maleate-induced renal damage, a model associated with oxidative stress. However, the mechanisms involved in curcumin protective effect were not explored, to assess this issue, curcumin was administered daily by gavage (150 mg/kg) five days before a single maleate (400 mg/kg)-injection. Curcumin prevented maleate-induced proteinuria, increased heat shock protein of 72 KDa (Hsp72) expression, and decreased plasma glutathione peroxidase activity. Maleate-induced oxidative stress by increasing the nicotinamide–adenine dinucleotide phosphate oxidase 4 (NOX4) and mitochondrial complex I-dependent superoxide anion (O2•—) production, formation of malondialdehyde (MDA)- and 3-nitrotyrosine (3-NT)-protein adducts and protein carbonylation and decreased GSH/GSSG ratio. Curcumin treatment ameliorated all the above-described changes. The maleate-induced epithelial damage, evaluated by claudin-2 and occludin expressions, was ameliorated by curcumin. It was found that maleate-induced oxidative stress promoted mitochondrial fission, evaluated by dynamin-related protein (Drp) 1 and fission (Fis) 1 expressions and by electron-microscopy, and autophagy, evaluated by phospho-threonine 389 from p70 ribosomal protein S6 kinase (p-Thr 389 p70S6K), beclin 1, microtubule-associated protein 1A/1B-light chain 3 phosphatidylethanolamine conjugate (LC3-II), autophagy-related gene 5 and 12 (Atg5-Atg12) complex, p62, and lysosomal-associated membrane protein (LAMP)-2 expressions in isolated proximal tubules and by electron-microscopy and LC-3 immunolabelling. Curcumin treatment ameliorated these changes. Moreover, curcumin alone induced autophagy in proximal tubules. These data suggest that the nephroprotective effect exerted by curcumin in maleate-induced renal damage is associated with decreased mitochondrial fission and autophagy.
KW - autophagy
KW - curcumin
KW - maleate
KW - mitochondrial fission
KW - oxidative stress
KW - renal damage
UR - http://www.scopus.com/inward/record.url?scp=84978879692&partnerID=8YFLogxK
U2 - 10.1002/biof.1313
DO - 10.1002/biof.1313
M3 - Artículo
SN - 0951-6433
VL - 42
SP - 686
EP - 702
JO - BioFactors
JF - BioFactors
IS - 6
ER -