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Expression of the receptor for advanced glycation end products in oligodendrocytes in response to oxidative stress
Author(s) -
Qin Jingdong,
Goswami Rajendra,
Dawson Sylvia,
Dawson Glyn
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21692
Subject(s) - rage (emotion) , neurodegeneration , oxidative stress , glycation , oligodendrocyte , receptor , microbiology and biotechnology , chemistry , biology , immunology , endocrinology , biochemistry , medicine , central nervous system , myelin , neuroscience , disease
Demyelination is a common result of oxidative stress in the nervous system, and we report here that the response of oligodendrocytes to oxidative stress involves the receptor for advanced glycation end products (RAGE). RAGE has not previously been reported in neonatal rat oligodendrocytes (NRO), but, by using primers specific for rat RAGE, we were able to show expression of messenger RNA (mRNA) for RAGE in NRO, and a 55‐kDa protein was detected by Western blotting with antibodies to RAGE. Neonatal rat oligodendrocytes stained strongly for RAGE, suggesting membrane localization of RAGE. Addition of low concentrations of hydrogen peroxide (100 μM) initiated 55‐kDa RAGE shedding from the cell membrane and the appearance of “soluble” 45‐kDa RAGE in the culture medium, followed by restoration of RAGE expression to normal levels. Increasing hydrogen peroxide concentration (>200 μM) resulted in no restoration of RAGE, and the cells underwent apoptosis and necrosis. We further confirmed the observation in a human oligodendroglioma‐derived (HOG) cell line. Both the antioxidant N‐acetyl‐L‐cysteine and the broad‐spectrum metalloproteases inhibitor TAPI0 were able partially to inhibit shedding of RAGE, suggesting involvement of metalloproteases in cleavage to produce soluble RAGE. The level of 55‐kDa RAGE in autopsy brain of patients undergoing neurodegeneration with accompanying inflammation [multiple sclerosis and neuronal ceroid‐lipofuscinosis (Batten's disease)] was much lower than that in age‐matched controls, suggesting that shedding of RAGE might occur as reactive oxygen species accumulate in brain cells and be part of the process of neurodegeneration. © 2008 Wiley‐Liss, Inc.