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Melatonin arrests peroxynitrite‐induced tau hyperphosphorylation and the overactivation of protein kinases in rat brain
Author(s) -
Yin Jun,
Liu YingHua,
Xu YaFei,
Zhang YongJie,
Chen JianGuo,
Shu BaiHua,
Wang JianZhi
Publication year - 2006
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2006.00343.x
Subject(s) - peroxynitrite , hyperphosphorylation , p38 mitogen activated protein kinases , chemistry , melatonin , phosphorylation , kinase , gsk 3 , protein kinase a , medicine , endocrinology , oxidative stress , microbiology and biotechnology , biochemistry , biology , superoxide , enzyme
Abstract: The purpose of this study was to examine the in vivo effect of melatonin (MEL) on peroxynitrite‐induced tau hyperphosphorylation and the involvement of glycogen synthase kinase‐3 β (GSK‐3 β ) and mitogen‐activated protein kinase (MAPK) families. Melatonin was injected into the right cerebroventricle of the rats 1 hr before the bilateral hippocampal injection of 3‐morpholino‐sydnonimine chloride (SIN‐1), the recognized donor of peroxynitrite. Thereafter, the phosphorylation level of tau and the activity of the kinases were analyzed. The injection of SIN‐1 induced hyperphosphorylation of tau at pS396 epitope with a concomitant activation of GSK‐3 β and selective MAPK isoforms including p38 α , p38 β , and p38 δ but not p38 γ . The effect of peroxynitrite was confirmed using uric acid, a recognized scavenger of peroxynitrite. Preinjection of MEL significantly arrested the peroxynitrite‐induced hyperphosphorylation of tau and the activation of GSK‐3 β and MAPKs. Melatonin also ameliorated peroxynitrite‐induced oxidative stress. We conclude that MEL can efficiently arrest peroxynitrite‐induced tau hyperphosphorylation, and the underlying mechanism may involve scavenging the reactive species and suppressing the activated GSK‐3 β and p38 MAPK family.