Insulin-like growth factor-1 protects against prion peptide-induced             cell death in neuronal cells via inhibition of Bax translocation.
Insulin-like growth factor-1 (IGF-1) is one of the most important components             of bovine colostrum. It exhibits antiapoptotic and antioxidative activities. Prion             diseases are neurodegenerative disorders caused by cell death through mitochondrial             dysfunction and increasing generation of reactive oxygen species (ROS). This study             examined the protective effect of IGF-1 on residues 106-126 of the cellular prion             protein [PrP (106-126)]-mediated mitochondrial neurotoxicity and oxidative stress.             In SH-SY5Y human neuronal cells, treatment with PrP (106-126) decreased the cell             viability and IGF-1 pretreatment markedly blocked the PrP (106-126)-induced neuronal             cell death. IGF-1 inhibited PrP (106-126)-induced intracellular ROS generation             and mitochondrial oxidative stress. In addition, IGF-1 blocked the translocation             of the Bax protein to the mitochondria induced by PrP (106-126). These results             demonstrate that IGF-1 protects neuronal cells against PrP (106-126)-mediated             neurotoxicity through an antioxidative effect and blockage of mitochondrial Bax             translocation. The results also suggest that regulation of IGF-1 secretion may             have a therapeutic potential in the management of mitochondrial dysfunction and             oxidative stress-induced neurodegeneration.
Korea Zoonoses Research Institute, Bio-Safety Research Institute,                     College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk                     561-756, Republic of Korea.
Yang-Gyu
YG
Park
Jae-Kyo
JK
Jeong
Myung-Hee
MH
Moon
Ju-Hee
JH
Lee
You-Jin
YJ
Lee
Jae-Won
JW
Seol
Shang-Jin
SJ
Kim
Seog-Jin
SJ
Kang
Sang-Youel
SY
Park
D000975:Antioxidants / Q000494:pharmacology* / Q000502:physiology; D017209:Apoptosis; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000502:physiology; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology*; D011328:Prions / Q000494:pharmacology / Q000502:physiology*; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D000975:Antioxidants; C494826:BAX protein, human; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011328:Prions; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C082632:prion protein (106-126); D007334:Insulin-Like Growth Factor I; D045304:Cytochromes c