Transduced human PEP-1-heat shock protein 27 efficiently protects against brain ischemic insult.

Abstract

Reactive oxygen species contribute to the development of various human diseases. Ischemia is characterized by both significant oxidative stress and characteristic changes in the antioxidant defense mechanism. Heat shock protein 27 (HSP27) has a potent ability to increase cell survival in response to oxidative stress. In the present study, we have investigated the protective effects of PEP-1-HSP27 against cell death and ischemic insults. When PEP-1-HSP27 fusion protein was added to the culture medium of astrocyte and primary neuronal cells, it rapidly entered the cells and protected them against cell death induced by oxidative stress. Immunohistochemical analysis revealed that, when PEP-1-HSP27 fusion protein was intraperitoneally injected into gerbils, it prevented neuronal cell death in the CA1 region of the hippocampus in response to transient forebrain ischemia. Our results demonstrate that transduced PEP-1-HSP27 protects against cell death in vitro and in vivo, and suggest that transduction of PEP-1-HSP27 fusion protein provides a potential strategy for therapeutic delivery in various human diseases in which reactive oxygen species are implicated, including stroke.

• Authors: Jae J An, Yeom P Lee, So Y Kim, Sun H Lee, Min J Lee, Min S Jeong, Dae W Kim, Sang H Jang, Ki-Yeon Yoo, Moo H Won, Tae-Cheon Kang, Oh-Shin Kwon, Sung-Woo Cho, Kil S Lee, Jinseu Park, Won S Eum, Soo Y Choi
• Journal: The FEBS journal (FEBS J) Vol. 275 Issue 6 Pg. 1296-308 (Mar 2008) ISSN: 1742-464X [Print] England
• PMID: 18279381 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HSP27 Heat-Shock Proteins
• HSPB1 protein, human
• Heat-Shock Proteins
• Molecular Chaperones
• Neoplasm Proteins
• Pep-1 peptide
• Peptides
• Reactive Oxygen Species
• Recombinant Fusion Proteins
• Cysteamine

Topics

• Animals
• Astrocytes (drug effects)
• Brain Infarction (prevention & control)
• Cell Death
• Cell Survival
• Cysteamine (analogs & derivatives, pharmacology, therapeutic use)
• Genetic Vectors (genetics)
• Gerbillinae
• HSP27 Heat-Shock Proteins
• Heat-Shock Proteins (genetics, pharmacology, therapeutic use)
• Hippocampus
• Humans
• Lipid Peroxidation
• Molecular Chaperones
• Neoplasm Proteins (genetics, pharmacology, therapeutic use)
• Neurons (drug effects)
• Oxidative Stress
• Peptides (genetics, pharmacology, therapeutic use)
• Reactive Oxygen Species (metabolism)
• Recombinant Fusion Proteins (genetics, pharmacology, therapeutic use)
• Transduction, Genetic