Effective delivery of Pep-1-cargo protein into ischemic neurons and long-term neuroprotection of Pep-1-SOD1 against ischemic injury in the gerbil hippocampus.

Abstract

We examined the intracellular delivery of Pep-1-cargo protein against transient ischemic damage in the hippocampal CA1 region in gerbils. For this study, we introduced green fluorescent protein (GFP) and constructed Pep-1-GFP protein. At 12h after Pep-1-GFP treatment, GFP fluorescence was shown in almost CA1 pyramidal neurons in ischemic animals; in the sham-operated group, GFP fluorescence was shown in a few pyramidal neurons. Next, we confirmed the long-term effects of Pep-1-Cu,Zn-superoxide dismutase 1 (SOD1) against ischemic damage. In behavioral test, locomotor activity was significantly increased in Pep-1- and Pep-1-SOD1-treated groups 1 day after ischemia/reperfusion; the locomotor activity in the Pep-1-treated group was higher than that of the Pep-1-SOD1-treated group. Thereafter, the locomotor activity in both groups was decreased with time. Four days after ischemia/reperfusion, the locomotor activity in the Pep-1-SOD1-treated group was similar to that of the sham group; in the Pep-1-treated group, the activity was lower than that of the sham group. In the histochemical study, the cresyl violet positive neurons in the Pep-1-SOD1-treated group were abundantly detected in the hippocampal CA1 region 5 days after ischemia/reperfusion. In biochemical study, SOD1 protein level and activity in all Pep-1-treated ischemic groups were significantly lower than that of the Pep-1-SOD1-treated group. Our results indicate that Pep-1-cargo fusion proteins can be efficiently delivered into neurons in the ischemic hippocampus, and that Pep-1-SOD1 treatment in ischemic animals show a neuroprotection in the ischemic hippocampus for a long time.

• Authors: Jun Hwi Cho, In Koo Hwang, Ki-Yeon Yoo, So Young Kim, Dae Won Kim, Young-Guen Kwon, Soo Young Choi, Moo-Ho Won
• Journal: Neurochemistry international (Neurochem Int) 2008 Mar-Apr Vol. 52 Issue 4-5 Pg. 659-68 ISSN: 0197-0186 [Print] England
• PMID: 17919780 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuroprotective Agents
• Pep-1 peptide
• Peptides
• Green Fluorescent Proteins
• Cysteamine
• Superoxide Dismutase
• Superoxide Dismutase-1

Topics

• Animals
• Brain (pathology)
• Brain Ischemia (drug therapy, pathology)
• Cell Death
• Cysteamine (administration & dosage, analogs & derivatives, pharmacology)
• Drug Delivery Systems
• Gerbillinae
• Green Fluorescent Proteins (metabolism)
• Hippocampus (pathology)
• Ischemic Attack, Transient (drug therapy, pathology)
• Male
• Motor Activity (drug effects)
• Neurons (pathology)
• Neuroprotective Agents
• Peptides (administration & dosage, pharmacology)
• Superoxide Dismutase (administration & dosage, pharmacology)
• Superoxide Dismutase-1