Vitamin E inhibits activated chaperone-mediated autophagy in rats with status epilepticus.
Seizures and status epilepticus induce an excessive production of reactive oxygen species leading to oxidative stress. Vitamin E, a classic antioxidant, has a neuroprotective effect on rats with seizures by regulating reactive oxygen species production. The activity of chaperone-mediated autophagy, a selective pathway for the degradation of cytosolic proteins in lysosomes, is enhanced during oxidative stress. Whether chaperone-mediated autophagy is induced during status epilepticus is not established. To address this problem, we used pilocarpine to elicit status epilepticus in rats. Lysosome-associated membrane protein 2a was used to estimate chaperone-mediated autophagy. We showed that compared to control animals, lysosome-associated membrane protein 2a at lysosomal membranes increased significantly in rats at 8 h, 16 h, and 24 h after induction of status epilepticus, which directly correlated with chaperone-mediated autophagy activity. Since reactive oxygen species are believed to be important in the pathogenesis of status epilepticus and are essential for the process of chaperone-mediated autophagy, we also sought to determine if pretreatment with vitamin E reduced chaperone-mediated autophagy. Pretreatment with vitamin E reduced oxidative stress and partially inhibited chaperone-mediated autophagy in brain at 24 h after status epilepticus versus vehicle. Taken together, these data show that chaperone-mediated autophagy is increased in rats with pilocarpine-induced status epilepticus through upregulation of de novo synthesis of lysosome-associated membrane protein 2a. Antioxidants such as vitamin E may partially inhibit activated chaperone-mediated autophagy.
Cao
L
L
Department of Neurology, Qilu Hospital of Shandong University, Jinan 250012, China.
Chen
R
R
Xu
J
J
Lin
Y
Y
Wang
R
R
Chi
Z
Z
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D006624:Hippocampus / Q000378:metabolism; D052119:Lysosomal-Associated Membrane Protein 2 / Q000096:biosynthesis*; D008297:Male; D018832:Molecular Chaperones / Q000096:biosynthesis*; D018384:Oxidative Stress; D010862:Pilocarpine; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D052119:Lysosomal-Associated Membrane Protein 2; D018832:Molecular Chaperones; D012333:RNA, Messenger; D010862:Pilocarpine; D014810:Vitamin E