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Abstract: SA-PO225

Role of Ceruloplasmin in Diabetic Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Prabhakar, Sharma S., Texas Tech University Health Sciences Center, Lubbock, Texas, United States
  • Deshmukh, Hemalata, Texas Tech University Health Sciences Center, Lubbock, Texas, United States
Background

We have previously demonstrated that diabetic nephropathy (DN) is associated with oxidative stress and decreased renal nitric oxide (NO) levels (Prabhakar et al JASN 2007). While many factors such as hyperglycemia, reactive oxygen species and angiotensin may account for inhibition of NO in DN, the exact mechanism remains unclear. Ceruloplasmin (Cp) is a copper-transporting protein that was incriminated in many glomerular diseases including Lupus nephritis and Ig A nephropathy. Increased urinary excretion of Cp has been proposed as an early biomarker of DN but the precise role of Cp in DN has not been studied. We hypothesized that diabetic kidneys may overexpress Cp which might play a role in the pathogenesis of DN.

Methods

To test our hypothesis we used ZSF rats, an established rat model of nephropathy of diabetes. They were studied from 8th week until 40 weeks. Both male and female rats were used while CD rats were used as non-diabetic controls. ZSF rats were fed a high fat high calorie (Purina 5008) diet,to maintain hyperglycemia while CD rats were fed normal rat chow. At 40 weeks all rats were euthanized, kidneys harvested, and homogenates used to examine the expression of Cp by western blot technique. Blood and urine samples were collected at the start and end of the study to evaluate the kidney function.

Results

By 12 weeks of age ZSF rats developed obesity, diabetes, hypertriglyceridemia, hypertension and proteinuric renal failure while CD rats remained nondiabetic without hypertension, obesity or kidney involvement. Male ZSF rats were heavier than females (650 gm vs 510 gm) and more hyperglycemic (295 mg/dl vs.210 mg/dl) while proteinuria and azotemia were also more severe in male ZSF rats. Expression of Cp was increased in the kidneys of ZSF rats (male more than female) compared to CD rats.

Conclusion

We conclude that rat kidneys with experimental DN overexpress Cp. Since Cp is involved in metabolizing NO to nitrosothiols, Cp may contribute to oxidative/nitrosative stress and progression of DN. Additional studies are in progress to further explore the role of Cp in DN in our model. Cp could play a pathogenic role in and could also be a biomarker of DN.

Funding

  • Private Foundation Support