Persistent phosphorylation of NKCC1 and WNK1 in the epicenter of the spinal cord following contusion injury

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• 作者：Hyun Kyung Lee ; BS^a ; Mostafa M. Ahmed ; MD^a ; Kevin C. King ; BS^a ; Gurwattan S. Miranpuri ; PhD^a ; Kristopher T. Kahle ; MD ; PhD^b ; Daniel K. Resnick ; MD^a ; ^{resnick@neurosurgery.wisc.edu" class="auth_mail} ; Dandan Sun ; MD ; PhD^a ; ^c
• 关键词：Contusive spinal cord injury ; NKCC1 ; WNK1
• 刊名：The Spine Journal
• 出版年：1 May, 2014
• 年：2014
• 卷：14
• 期：5
• 页码：777-781
• 全文大小：457 K

文摘

Background context

NKCC1 regulates neuronal homeostasis of chloride ions and mediates GABAergic activities in nociceptive processing. WNK1 is an upstream regulator of NKCC1 and acts via SPAK (STE20/SPS1-related proline/alanine-rich kinase) and oxidative stress-responsive kinase 1. NKCC1 activity has been shown to be important in edema formation and nociception following spinal cord injury (SCI).

Purpose

To determine the role of NKCC1 and WNK1 in spinal cord tissues in the acute and chronic phases following contusional SCI.

Study design

An experimental study investigating the phosphorylation profile of an important Cl-regulatory protein Na+-K+-Cl鈭?cotransporter 1 (NKCC1) and its regulatory-kinase WNK1 (kinase with-no-lysine).

Methods

Sprague-Dawley rats underwent a contusive SCI at T9. The epicenter spinal cord tissues were harvested at Days 1, 3, and 7 for acute phase of injury or Days 35 and 42 in the chronic phase of injury. Western blot was used to compare phosphorylated levels of both NKCC1 and WNK1 in injured tissues compared with those of sham.

Results

A sustained increase in phosphorylation of NKCC1 and WNK1 was detected in the lesion epicenter in spinal cord during both acute and chronic phases following SCI.

Conclusions

These results suggest that persistent activation of NKCC1 and WNK1 may play an important role in SCI.