Nicotine reduces the cytotoxic effect of glycated proteins on microglial cells.
Protein glycation has been implicated to play an important role in the pathogenesis of Alzheimer's disease and other neurological disorders. Glycation induces extensive change in the structure of proteins and leads to the formation of cross beta-structures which are detected by the receptor of AGE. Activation of these receptors by glycated proteins transduces the signaling pathways which contribute to neuronal malfunctions and death. Glycated proteins can induce activation of microglia, which exacerbate the pathology of Alzheimer's disease by causing chronic inflammation. Compounds which can decelerate glycation or prevent the structural change of proteins during glycation should be of therapeutic interest. In this study the effect of nicotine on protein glycation and structural alterations of the glycated protein were investigated. Bovine serum albumin, as a model protein, was glycated by glucose in the presence or absence of nicotine and structural changes in the protein together with the effect of glycated proteins on the activation of microglia via receptor of AGE were studied. Nicotine not only could not prevent glycation, but even increased protein glycation. However, proteins glycated in the presence of nicotine did not form beta-structures. In the absence of this secondary structure glycated proteins cannot bind to the receptor of AGE on microglia. Here we showed that glycated proteins prepared in the presence of nicotine could not activate microglial cells.
Khazaei
Mohammad R
MR
School of Biology, College of Science, University of Tehran, Tehran, Iran.
Bakhti
Mostafa
M
Habibi-Rezaei
Mehran
M
D000818:Animals; D000831:Animals, Newborn; D002942:Circular Dichroism; D005947:Glucose / Q000378:metabolism*; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism
D009419:Nerve Tissue Proteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009538:Nicotine; D005947:Glucose