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P4‐144: Loose membrane‐bound endogenous factors might modulates the intramembrane cleavages of βAPP
Author(s) -
Mori Kohji,
Okochi Masayasu,
Tagami Shinji,
Funamoto Satoru,
Kodama Takashi S.,
Yanagida Kanta,
Nakayama Taisuke,
Tatsumi Shinichi,
Fukumori Akio,
Tanimukai Hitoshi,
Tanaka Toshihisa,
Hashimoto Ryota,
Morihara Takashi,
Ihara Yasuo,
Kudo Takashi,
Takeda Masatoshi
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.812
Subject(s) - cleavage (geology) , presenilin , endogeny , chemistry , in vitro , microbiology and biotechnology , in vivo , biochemistry , biology , alzheimer's disease , medicine , disease , paleontology , fracture (geology)
Mitochondria were isolated according to Rajapakse et al. (2001). M-aconitase activity was measured by monitoring formation of cis-aconitate at 240 nM. Results: In the more damaged FC of SFAD and AD brain, the enzyme activity was decreased compared with Co region whereas in the less damaged OPC of SFAD and AD brain the parameter was not changed. Oxidants Ab(25-35), H2O2 and homocysteine (Hcy) dose-dependently inhibited maconitase. In Co FC, maximal inhibitory effect increased in sequence: 0.5 mM Hcy (15%) < 1mM H2O2 (34%) < 0.001 mM Ab(25-35) (40%). In AD FC, Ab(25-35) and H2O2 induced weaker enzyme inhibition (26%) than in Co FC whereas in SFAD FC inhibition was lowest (18%). Co and AD brain OPC showed lower inhibition of m-aconitase by oxidants than FC. SFAD brain revealed no regional difference of inhibition. In contrast to oxidants, the antioxidants melatonin (Mel), glutathione (GSH) and 17b-estradiol (17bE) stimulated m-aconitase in Co, AD and SFAD brain. In Co FC, maximal stimulatory effect increased in sequence: 0.01 mM 17bE (21%) < 1.0 mM GSH (46 %) < 0.01 mM Mel (67%). In SFAD FC, the effects were weaker than in Co FC. In OPC, antioxidant-induced stimulation of m-aconitase did not differ significantly from that in FC. Conclusions: Thus, m-aconitase of human brain reveals opposite response to endogenous proand antioxidants. The mitochondrial oxidant-antioxidant relationship may play a principal role in the regulation of m-aconitase activity and, thereby, Krebs cycle rate in aged, AD and SFAD brain regions.