Role of sterile 20/sps1-related proline/alanine-rich kinase in mice with endotoxic shock

Abstract

Background: Na+-K+-2Cl− co-transporters (NKCCs) are involved in the regulation of permeability and tissue edema during sepsis. Inhibition of NKCC can reduce inflammation, edema formation, and bacterial burden. STE20/SPS1-realted proline/alanine-rich kinase (SPAK) is known to phosphorylate and activate NKCCs. However, there is no data regarding the role of SPAK in the pathological responses of sepsis. Therefore, the aim of this study was to examine the changes of systemic responses to endotoxemia in SPAK knockout mice. Materials and Methods: Wild-type and SPAK knockout mice were randomly given with vehicle (saline) or Escherichia coli lipopolysaccharide (LPS, 50 mg/kg) and monitored for 24 h. The alterations of hemodynamics, blood glucose, biochemical variables, plasma nitric oxide (NO) levels, blood flow, superoxide levels, and survival rate were analyzed during the experimental period. Results: In this study, LPS induced circulatory failure, hypoglycemia, multiple organ dysfunction, and mortality in wild-type mice. The NO levels of plasma were augmented and blood flow of the tongue, palm, sole, and abdomen were reduced in wild-type mice with endotoxic shock. However, there were no significant differences in these functional parameters and survival rate between wild-type and SPAK knockout mice with endotoxemia. Conclusions: These results demonstrate that inhibition of SPAK did not improve circulatory failure, hypoglycemia, multiple organ dysfunction, or mortality in mice that treated LPS. Thus, it seems that SPAK may not play an important role in endotoxic shock.

Keywords

• STE20/SPS1-realted proline/alanine-rich kinase
• endotoxic shock
• multiple organ dysfunction syndrome
• nitric oxide
• superoxide