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The role of phosphodiesterase 3 in endotoxin-induced acute kidney injury

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Author(s)
Won-Il ChoiKun Young KwonJeong Wook SeoJohn BeagleDeborah A QuinnCharles A Hales
Keimyung Author(s)
Choi, Won IlKwon, Kun Young
Department
Dept. of Internal Medicine (내과학)
Dept. of Pathology (병리학)
Institute for Medical Science (의과학연구소)
Journal Title
BMC Infectious Diseases
Issued Date
2009
Volume
9
Issue
1
Abstract
Background
Acute kidney injury frequently accompanies sepsis. Endotoxin is known to reduce tissue levels of cAMP and low levels of cAMP have been associated with renal injury. We, therefore, hypothesized that endotoxin induced renal injury by activating phosphodiesterase 3 (PDE3) which metabolizes cAMP and that amrinone an inhibitor of PDE3 would prevent the renal injury.


Methods

Animals were divided into three groups (n = 7/group): 1) Control (0.9% NaCl infusion without LPS); 2) LPS (0.9% NaCl infusion with LPS); 3) Amrinone+LPS (Amrinone infusion with LPS). Either lipopolysaccharide (LPS) or vehicle was injected via the jugular vein and the rats followed for 3 hours. We explored the expression of PDE3 isoenzymes and the concentrations of cAMP in the tissue.


Results

The PDE3B gene but not PDE3A was upregulated in the kidney of LPS group. Immunohistochemistry also showed that PDE3B was expressed in the distal tubule in the controls and LPS caused PDE3B expression in the proximal as well. However, PDE3A was not expressed in the kidney either in the control or LPS treated groups. Tissue level of cAMP was decreased after LPS and was associated with an increase in blood urea nitrogen, creatinine, ultrastructural proximal tubular changes, and expression of inducible nitric oxide synthase (iNOS) in the endotoxemic kidney. In septic animals the phosphodiesterase 3 inhibitor, amrinone, preserved the tissue cAMP level, renal structural changes, and attenuated the increased blood urea nitrogen, creatinine, and iNOS expression in the kidney.


Conclusion

These findings suggest a significant role for PDE3B as an important mediator of LPS-induced acute kidney injury.
Keimyung Author(s)(Kor)
최원일
권건영
Publisher
School of Medicine
Citation
Won-Il Choi et al. (2009). The role of phosphodiesterase 3 in endotoxin-induced acute kidney injury. BMC Infectious Diseases, 9(1), 80–80. doi: 10.1186/1471-2334-9-80
Type
Article
ISSN
1471-2334
DOI
10.1186/1471-2334-9-80
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35242
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
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