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• W96778056 abstract "Absence of the p62 gene in mouse brain leads to biochemical and cognitive deficits that resemble Alzheimer’s disease (AD). In this context, the objective of this study was to examine the age-associated oxidative damage to the p62 promoter in AD. Increased 8-OHdG staining, a marker of oxidative stress, was observed in brain sections from mice deficient in the p62 gene compared to control. Treatment of MEF cells deficient in p62 with H2O2 resulted in decreased cell survival and an absence of Nrf2 nuclear translocation. The mouse p62 promoter exhibited elevated oxidative damage with increasing age and the degree of p62 promoter damage was also age-correlated in human brain samples. In human subjects, the expression of p62 was decreased in AD brain relative to age-matched controls, and likewise decreased p62 expression correlated with oxidative damage to the promoter. Treatment of HEK cells with H2O2 resulted in decreased p62 expression concomitant with increased promoter damage. Consistent with these findings, a transgenic AD mouse model also exhibited increased p62 promoter * Published in Free Radic. Biol. Med. 46, 492-501, 2009. 95 damage and reduced p62 levels in brain. Altogether, our results reveal that oxidative damage to the p62 promoter correlates with decreased expression of p62 and may contribute to age-associated neurodegenerative disease such as AD and others. INTRODUCTION Oxidative stress is the result of imbalance between productions of reactive oxygen species (ROS) and a biological system's ability to detoxify the reactive intermediates or repair the oxidative damage. Low levels of ROS can act as signaling molecules in various intracellular processes (Scherz-Shouval and Elazar, 2007). However, when the ROS level overwhelms the antioxidant and repair system, cells might be damaged by these molecules. Progressive and irreversible accumulation of oxidative damage contributes to the aging process, and is thus implicated in development of several age-associated diseases, such as neurodegenerative diseases (Filipcik et al., 2006). Oxidative damage to DNA is particularly harmful since it may cause mutations that can be inherited by the next generation, leading to genome instability. Among the five nucleobases, guanine is the most susceptible to oxidation because of its high electron density (Steenken, 1989). The predominant DNA oxidative adduct is 8-hydroxydeoxyguanosine (8-OHdG), which serves as a common biomarker of DNA oxidative damage (Steenken, 1989; Kasai, 1997). Most 8-OHdG lesions are repaired by a base excision repair (BER) pathway. It has been reported that when the ability of the repair system declines, cumulative oxidative DNA damage in the mitochondria and nuclear genomes of neurons may play a critical role in brain aging and neurodegenerative disorders such as AD, Parkinson’s disease and 96 Amyotrophic Lateral Sclerosis (Markesbery and Lovell, 2006; Nakabeppu et al., 2007; Warita et al., 2001). Relationships have been established among increased DNA damage, defective DNA repair, aging, and age-associated neurodegenerative disease (Lovell and Markesbery, 2007; Kikuchi et al., 2002; Martien and Abbadie, 2007). However, the exact mechanism by which oxidative DNA damage lead to neurodegeneration or neuronal cell death still remains obscure. Human p62 is oxidatively-induced in human and mouse cell lines (Ishii et al., 1997), and the p62 protein has been localized to aggresomes of various neurodegenerative diseases (Zatloukal et al., 2002). This gene was first identified by Park et al., as the ligand for the p56 (Park et al.,2002), and referred to as Sequestosome 1/SQSTM1. In humans, variants of p62/SQSTM1 have been linked to Pagets Disease of Bone (Layfield and Hocking, 2004). In mouse, the gene is related to A170/STAP (Signal Transduction Adapter Protein (Okazaki et al., 1999); whereas in rat, the gene is referred to as ZIP, the zeta interacting partner of the atypical protein kinase C (Puls et al., 1997). The p62 protein contains several interaction motifs that endow the protein with scaffolding abilities (Moscat et al., 2007). At its C-terminal tail p62 possesses an ubiquitin associated domain that interacts with K63 polyubiquitin chains and the N- terminus possesses a PB1 domain. A ZZ-finger recruits the atypical PKC and other proteins, whereas the TRAF6 binding site (TBS) recruits the E3 ubiquitin ligase TRAF6. Functionally, p62 serves to connect signaling pathways associated with two post- translational modifications. An absence of p62 leads to the loss of aggresomes and neuronal cell death (Nakaso et al., 2004). Moreover, p62 has been reported to activate the" @default.
• W96778056 created "2016-06-24" @default.
• W96778056 creator A5032334740 @default.
• W96778056 date "2009-06-30" @default.
• W96778056 modified "2023-09-24" @default.
• W96778056 title "Regulation of the p62 promoter by oxidative damage in neurodegenerative disease and aging" @default.
• W96778056 cites W1504816243 @default.
• W96778056 cites W1542215809 @default.
• W96778056 cites W1549869862 @default.
• W96778056 cites W1939228490 @default.
• W96778056 cites W1965158726 @default.
• W96778056 cites W1967464880 @default.
• W96778056 cites W1967874462 @default.
• W96778056 cites W1967899016 @default.
• W96778056 cites W1970791359 @default.
• W96778056 cites W1973207539 @default.
• W96778056 cites W1976067097 @default.
• W96778056 cites W1978651752 @default.
• W96778056 cites W1979369962 @default.
• W96778056 cites W1984433129 @default.
• W96778056 cites W1986083613 @default.
• W96778056 cites W1991883957 @default.
• W96778056 cites W1995771017 @default.
• W96778056 cites W1996037209 @default.
• W96778056 cites W2002288000 @default.
• W96778056 cites W2005997790 @default.
• W96778056 cites W2010352524 @default.
• W96778056 cites W2014918593 @default.
• W96778056 cites W2018183878 @default.
• W96778056 cites W2022325384 @default.
• W96778056 cites W2023542615 @default.
• W96778056 cites W2026048677 @default.
• W96778056 cites W2026938943 @default.
• W96778056 cites W2028243150 @default.
• W96778056 cites W2030625746 @default.
• W96778056 cites W2033832481 @default.
• W96778056 cites W2035506508 @default.
• W96778056 cites W2036997305 @default.
• W96778056 cites W2037158293 @default.
• W96778056 cites W2037160815 @default.
• W96778056 cites W2045763473 @default.
• W96778056 cites W2047428823 @default.
• W96778056 cites W2049557390 @default.
• W96778056 cites W2052659766 @default.
• W96778056 cites W2054874422 @default.
• W96778056 cites W2055432326 @default.
• W96778056 cites W2056648984 @default.
• W96778056 cites W2057047426 @default.
• W96778056 cites W2058966851 @default.
• W96778056 cites W2061259632 @default.
• W96778056 cites W2066170631 @default.
• W96778056 cites W2070835061 @default.
• W96778056 cites W2071850731 @default.
• W96778056 cites W2080444376 @default.
• W96778056 cites W2081106067 @default.
• W96778056 cites W2084129838 @default.
• W96778056 cites W2085481317 @default.
• W96778056 cites W2087249338 @default.
• W96778056 cites W2089038479 @default.
• W96778056 cites W2090825344 @default.
• W96778056 cites W2102430316 @default.
• W96778056 cites W2107114877 @default.
• W96778056 cites W2118898883 @default.
• W96778056 cites W2119399459 @default.
• W96778056 cites W2119637022 @default.
• W96778056 cites W2120640283 @default.
• W96778056 cites W2121642311 @default.
• W96778056 cites W2121966499 @default.
• W96778056 cites W2124263476 @default.
• W96778056 cites W2124595524 @default.
• W96778056 cites W2125123150 @default.
• W96778056 cites W2127761639 @default.
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• W96778056 cites W2146124002 @default.
• W96778056 cites W2147984935 @default.
• W96778056 cites W2152165298 @default.
• W96778056 cites W2157535220 @default.
• W96778056 cites W2166376601 @default.
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