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PKC delta and NADPH oxidase in neuronal sensitivity to glycoxidative stress
Author(s) -
Nitti Mariapaola,
Furfaro AnnaLisa,
Traverso Nicola,
Odetti Patrizio,
Storace Daniela,
Cottalasso Damiano,
Pronzato Maria Adelaide,
Marinari Umberto Maria,
Domenicotti Cinzia
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a24-a
Subject(s) - nadph oxidase , oxidative stress , rage (emotion) , glycation , chemistry , sh sy5y , receptor , endocrinology , medicine , retinoic acid , superoxide , protein kinase c , microbiology and biotechnology , cell culture , signal transduction , biology , enzyme , biochemistry , neuroblastoma , gene , neuroscience , genetics
Advanced Glycation End product (AGE) accumulation in brain is believed to contribute to neuronal death in several neurodegenerative diseases. The activation of RAGE (receptor for AGE) has been demonstrated to play an essential role in the induction of oxidative stress. In this work we demonstrate that AGE‐induced neuronal injury is related to PKC delta‐dependent activation of NADPH oxidase. SH‐SY5Y neuroblastoma cells untreated or treated with 10 μM retinoic acid (RA) were exposed to glycated albumin (AGE‐BSA). After 24 h of AGE exposure the viability of RA treated cells was decreased by 35 %, while untreated cells were almost resistant to AGEs. Interestingly, analysis of ROS levels showed that AGE‐BSA was able to induce an overproduction of peroxides and superoxide in RA‐treated cells. The marked sensitivity of RA treated cells was accompanied by a 2.5 fold increase in p47 phox expression and a 40% increase in PKC delta activity. In addition, the overexpression of PKC delta in undifferentiated SH‐SY5Y cells increased their susceptibility to AGE‐induced damage as well as it has been described in differentiated cells. These observations may have interesting consequences for the clinical approach to human neurodegenerative diseases. Grants from PRIN n. 2004063943_001 and n. 2004068552_002