JNK activation contributes to DP5 induction and apoptosis following traumatic spinal cord injury

Ke Jie Yin, Gyeong Moon Kim, Jin Moo Lee, Yong Y. He, Jan Xu, Chung Y. Hsu

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Growing evidence suggests that cells undergo apoptosis after spinal cord injury (SCI). However, little is known about the early events that trigger apoptosis in the contused cord. The BH3-only subfamily of pro-apoptotic regulators (e.g., bim, bad, and dp5) is recognized as initiators of the apoptotic cascade, and is subject to stringent control, both at the transcriptional and post-translational level. In the current study, we studied upstream events regulating trauma-induced apoptosis in the spinal cord. Within 1 h after SCI in rats, DP5 was induced, while Bim and Bad levels remained unchanged. In parallel, SCI also activated the stress-induced c-Jun N-terminal kinase (JNK), leading to the phosphorylation of c-Jun, with a similar temporal profile. Immunohistochemical analysis revealed that p-JNK and DP5 colocalized to neurons and oligodendrocytes undergoing apoptosis in the injured cord, but were absent in uninjured spinal cord. Furthermore, inhibition of JNK activity with in vivo delivery of SP600125 or a jnk1 antisense oligodeoxynucleotide (ODN) attenuated DP5 induction and caspase-3 activation. These results suggest that JNK activation contributes to trauma-induced DP5 expression and subsequent apoptosis in SCI.

Original languageEnglish
Pages (from-to)881-889
Number of pages9
JournalNeurobiology of Disease
Volume20
Issue number3
DOIs
Publication statusPublished - Dec 2005

Fingerprint

Spinal Cord Injuries
Phosphotransferases
Apoptosis
Spinal Cord
JNK Mitogen-Activated Protein Kinases
Contusions
Oligodeoxyribonucleotides
Oligodendroglia
Wounds and Injuries
Caspase 3
Phosphorylation
Neurons

Keywords

  • Apoptosis
  • BH3-only family
  • Caspase 3
  • DP5
  • JNK
  • Spinal cord injury

ASJC Scopus subject areas

  • Neurology

Cite this

JNK activation contributes to DP5 induction and apoptosis following traumatic spinal cord injury. / Yin, Ke Jie; Kim, Gyeong Moon; Lee, Jin Moo; He, Yong Y.; Xu, Jan; Hsu, Chung Y.

In: Neurobiology of Disease, Vol. 20, No. 3, 12.2005, p. 881-889.

Research output: Contribution to journalArticle

Yin, Ke Jie ; Kim, Gyeong Moon ; Lee, Jin Moo ; He, Yong Y. ; Xu, Jan ; Hsu, Chung Y. / JNK activation contributes to DP5 induction and apoptosis following traumatic spinal cord injury. In: Neurobiology of Disease. 2005 ; Vol. 20, No. 3. pp. 881-889.
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