17β-Estradiol Inhibits Apoptotic Cell Death of Oligodendrocytes by Inhibiting RhoA-JNK3 Activation after Spinal Cord Injury
| Autor: | Tae Young Yune, Soo Young Choi, Jee Youn Lee, Tae H. Oh |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Programmed cell death RHOA Blotting Western Estrogen receptor Apoptosis Neuroprotection Rats Sprague-Dawley Endocrinology Mitogen-Activated Protein Kinase 10 Internal medicine In Situ Nick-End Labeling Animals Estrogen Receptor beta Medicine Spinal cord injury Cells Cultured Spinal Cord Injuries Behavior Animal Estradiol biology Caspase 3 Reverse Transcriptase Polymerase Chain Reaction business.industry Estrogen Receptor alpha medicine.disease Spinal cord Caspase 9 Oligodendrocyte Enzyme Activation Oligodendroglia medicine.anatomical_structure biology.protein rhoA GTP-Binding Protein business |
| Zdroj: | Endocrinology. 153:3815-3827 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2012-1068 |
| Popis: | A delayed oligodendrocyte cell death after spinal cord injury (SCI) contributes to chronic demyelination of spared axons, leading to a permanent neurological deficit. Therefore, therapeutic approaches to prevent oligodendrocyte cell death after SCI should be considered. Estrogens are well known to have a broad neuroprotective effect, but the protective effect of estrogens on oligodendrocytes after injury is largely unknown. Here, we demonstrated that 17β-estradiol attenuates apoptosis of oligodendrocytes by inhibiting RhoA and c-Jun-N-terminal kinase activation after SCI. Estrogen receptor (ER)-α and -β were expressed in oligodendrocytes of the spinal cord, and 17β-estradiol treatment significantly inhibited oligodendrocyte cell death at 7 d after injury as compared with vehicle (cyclodextrin) control. 17β-Estradiol also attenuated caspase-3 and -9 activation at 7 d and reduced the loss of axons from progressive degeneration. In addition, 17β-estradiol inhibited RhoA and JNK3 activation, which were activated and peaked at 3 and/or 5 d after injury. Furthermore, administration of Rho inhibitor, PEP-1-C3 exoenzyme, inhibited RhoA and JNK3 activation, and decreased phosphorylated c-Jun level at 5 d after injury. Additionally, the attenuation of RhoA and JNK3 activation as well as oligodendrocyte cell death by 17β-estradiol was reversed by ER antagonist, ICI182780. Our results thus indicate that 17β-estradiol treatment improves functional recovery after SCI in part by reducing oligodendrocyte cell death via inhibition of RhoA and JNK3 activation, which were ER dependent. Furthermore, improvement of hindlimb motor function by posttreatment of 17β-estradiol suggests its potential as a therapeutic agent for SCI patients. |
| Databáze: | OpenAIRE |
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