Huperzine A protects isolated rat brain mitochondria against beta-amyloid peptide.
Our previous work in cells and animals showed that mitochondria are involved in the neuroprotective effect of huperzine A (HupA). In this study, the effects of HupA on isolated rat brain mitochondria were investigated. In addition to inhibiting the Abeta(25-35) (40 microM)-induced decrease in mitochondrial respiration, adenosine 5'-triphosphate (ATP) synthesis, enzyme activity, and transmembrane potential, HupA (0.01 or 0.1 microM) effectively prevented Abeta-induced mitochondrial swelling, reactive oxygen species increase, and cytochrome c release. More interestingly, administration of HupA to isolated mitochondria promoted the rate of ATP production and blocked mitochondrial swelling caused by normal osmosis. These results indicate that HupA protects mitochondria against Abeta at least in part by preserving membrane integrity and improving energy metabolism. These direct effects on mitochondria further extend the noncholinergic functions of HupA.
Gao
Xin
X
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, People's Republic of China.
Zheng
Chun Yan
CY
Yang
Ling
L
Tang
Xi Can
XC
Zhang
Hai Yan
HY
D000255:Adenosine Triphosphate / Q000378:metabolism; D000470:Alkaloids; D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000502:physiology / Q000648:ultrastructure; D016923:Cell Death; D019069:Cell Respiration; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D019610:Cytoprotection; D005609:Free Radicals; D032501:Huperzia / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000502:physiology; D010085:Oxidative Phosphorylation; D010446:Peptide Fragments / Q000378:metabolism*; D008517:Phytotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000627:therapeutic use*
D000470:Alkaloids; D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D005609:Free Radicals; D010446:Peptide Fragments; D012717:Sesquiterpenes; C113042:amyloid beta-protein (31-35); C050426:huperzine A; D000255:Adenosine Triphosphate