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


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


METHODS
An experimental study investigating the phosphorylation profile of an important Cl-regulatory protein Na+-K+-Cl- 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.
Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Box 8600 Clinical Science Center, 600 Highland Ave., Madison, WI 53792, USA.
Hyun Kyung
HK
Lee
Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Box 8600 Clinical Science Center, 600 Highland Ave., Madison, WI 53792, USA.
Mostafa M
MM
Ahmed
Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Box 8600 Clinical Science Center, 600 Highland Ave., Madison, WI 53792, USA.
Kevin C
KC
King
Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Box 8600 Clinical Science Center, 600 Highland Ave., Madison, WI 53792, USA.
Gurwattan S
GS
Miranpuri
Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Parkman St, Boston, MA 02114, USA.
Kristopher T
KT
Kahle
Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Box 8600 Clinical Science Center, 600 Highland Ave., Madison, WI 53792, USA. Electronic address: resnick@neurosurgery.wisc.edu.
Daniel K
DK
Resnick
Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Box 8600 Clinical Science Center, 600 Highland Ave., Madison, WI 53792, USA; Waisman Center, 1500 Highland Ave, Madison, WI 53705, USA.
Dandan
D
Sun
D000208:Acute Disease; D000818:Animals; D015153:Blotting, Western; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D015778:Minor Histocompatibility Antigens; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism*; D015854:Up-Regulation; D000076204:WNK Lysine-Deficient Protein Kinase 1
D015778:Minor Histocompatibility Antigens; D064506:Solute Carrier Family 12, Member 2; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C410410:Wnk1 protein, rat
Contusive spinal cord injury; NKCC1; WNK1