Systemic administration of PEP-1-SOD1 fusion protein improves functional recovery by inhibition of neuronal cell death after spinal cord injury

Free Radical Biology & Medicine
Tae Young YuneTae Hwan Oh

Abstract

Spinal cord injury (SCI) produces excessive levels of reactive oxygen species (ROS) that induce apoptosis of neurons. Cu,Zn-superoxide dismutase (SOD1) is a key antioxidant enzyme that detoxifies intracellular ROS, thereby protecting cells from oxidative damage. PEP-1 is a peptide carrier capable of delivering full-length native peptides or proteins into cells. In the study described here, we fused a human SOD1 gene with PEP-1 in a bacterial expression vector to produce a genetic in-frame PEP-1-SOD1 fusion protein; we then investigated the neuroprotective effect of the fusion protein after SCI. The expressed and purified PEP-1-SOD1 was efficiently delivered into cultured cells and spinal cords in vivo, and the delivered fusion protein was biologically active. Systemic administration of PEP-1-SOD1 significantly decreased levels of ROS and protein carbonylation and nitration in spinal motor neurons after injury. PEP-1-SOD1 treatment also significantly inhibited mitochondrial cytochrome c release and activation of caspase-9 and caspase-3 in spinal cords after injury. Furthermore, PEP-1-SOD1 treatment significantly reduced ROS-induced apoptosis of motor neurons and improved functional recovery after SCI. These results suggest that ...Continue Reading

References

Feb 1, 1995·Journal of Neurotrauma·D M BassoJ C Bresnahan
Feb 1, 1994·Journal of Leukocyte Biology·W O CarterJ P Robinson
Jan 1, 1996·Scientific American·S Grillner
Dec 20, 1995·Archives of Biochemistry and Biophysics·A DubeyR S Sohal
Aug 15, 1997·The Journal of Biological Chemistry·B S Berlett, E R Stadtman
Jul 29, 1998·Free Radical Biology & Medicine·D LiuJ Liu
Nov 11, 1998·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·M FujimuraP H Chan
Feb 3, 1999·Annals of the New York Academy of Sciences·L M Jordan
Jul 30, 1999·Nature Medicine·J E SpringerP E Knapp
Dec 29, 1999·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·N G FawellS S Scranton
Jun 30, 2000·Current Opinion in Cell Biology·A Prochiantz
Oct 12, 2000·Current Opinion in Biotechnology·M C MorrisG Divita
Nov 4, 2000·Journal of Neurotrauma·A LewénP H Chan
Nov 14, 2000·Brain Research·G A MetzK Fouad
Mar 22, 2001·Experimental Neurology·S D GrossmanJ R Wrathall
Feb 19, 2002·Current Opinion in Biotechnology·Jehangir S Wadia, Steven F Dowdy
Oct 9, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Taku SugawaraPak H Chan
Apr 5, 2003·Toxicology Letters·Csaba Szabó
Mar 6, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·David P StirlingWolfram Tetzlaff
Jun 17, 2004·Human Molecular Genetics·Houbo JiangJian Feng
Mar 21, 2006·Biochimica Et Biophysica Acta·Edwige GrosGilles Divita
Jun 27, 2006·Journal of Cellular and Molecular Medicine·Isabella Dalle-DonneAldo Milzani

❮ Previous
Next ❯

Citations

Jul 28, 2010·Endocrinology·John A Kessler
Jun 13, 2009·Journal of Neurochemistry·Tae Y YuneTae H Oh
Jun 22, 2019·Brain and Behavior·Jiaqi BiJianxiong Shen

❮ Previous
Next ❯

Related Concepts

Related Feeds

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Astrocytes in Repair & Regeneration

Astrocytes are glial cells found within the CNS and are able to regenerate new neurons. They become activated during CNS injury and disease. The activation leads to the transcription of new genes and the repair and regeneration of neurons. Discover the latest research on astrocytes in repair and regeneration here.

Barrel cortex

Here is the latest research on barrel cortex, a region of somatosensory and motor corticies in the brain, which are used by animals that rely on whiskers for world exploration.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis