Regulation of Inositol 1,4,5-triphosphate receptor, type 1 (IP3R1) in hypoxic/reperfusion injury of white matter

Varun Kesherwani, Sandeep K. Agrawal

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Objective: Calcium overloading is responsible for initiating the cell death in neuronal tissue after hypoxic injury. Inositol 1,4,5-triphosphate receptors (IP3Rs) is an important calcium channel which regulates cellular calcium homeostasis. IP3R1 is widely expressed in brain and spinal tissue. In the present study, we have studied the regulation of IP3R1 in hypoxic/reperfusion injury of spinal cord dorsal column in vitro. Methods: Dorsal columns were isolated from the spinal cord of adult rats and injury was induced by exposing to hypoxic condition for 1 hour. After injury, reperfusion was carried out for 0, 2, 4, and 8 hours. Tissues were collected and processed for western blotting, immunohistochemistry and real-time PCR. Results: In the present study, we have found increased expression of IP3R1 after hypoxic/reperfusion injury of spinal cord dorsal column in vitro. Maximum expression of IP3R1 has been seen at 4 hours after hypoxia. Double immunofluorescence studies show the localization of IP3R1 in axons and astrocytes. Further identifying the signaling pathway involved in the regulation, we found Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-62 and c-Jun N-terminal kinase (JNK) inhibitor SP600125 reduced the expression of IP3R1 suggesting the role of CaMKII and JNK in the regulation of IP3R1 expression. We did not find role of ERK and p38 in the regulation IP3R1 expression in hypoxic/reperfusion injury of dorsal column in vitro. Discussion: The result presented in this study showed that IP3R1 expression is increased in hypoxic/reperfusion injury of spinal cord white matter and it is regulated by the CaMKII-JNK pathway.

Original languageEnglish (US)
Pages (from-to)504-511
Number of pages8
JournalNeurological research
Volume34
Issue number5
DOIs
Publication statusPublished - Jun 1 2012

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Keywords

  • CaMKII/JNK pathway
  • Calcium
  • Dorsal column
  • Hypoxia/reperfusion
  • IP3R1
  • Spinal cord injury

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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