Abstract | BACKGROUND:
Nephrotic syndrome (NS) is associated with dysregulation of lipid/ lipoprotein metabolism and impaired high-density lipoprotein (HDL)-mediated reverse cholesterol transport and atherosclerosis. HDL serves as vehicle for transport of surplus lipids from the peripheral tissues for disposal in the liver via two receptors: (i) scavenger receptor class B type I (SR-BI) which serves as a docking receptor, enabling HDL to unload its lipid cargo and return to circulation to repeat the cycle, and (ii) beta chain ATP synthase which serves as the endocytic receptor mediating removal and catabolism of lipid-poor HDL. SR-BI abundance is regulated by PDZ-containing kidney protein 1 (PDZK1), a multifunctional protein, which prevents SRB-1 degradation at the post-translational level. This study explored the effect of NS on hepatic expression of these important molecules. METHODS: Gene expression, protein abundance and immunohistological appearance of the above proteins were measured in the liver of rats with puromycin-induced NS and control rats. RESULTS: CONCLUSIONS: NS results in elevation of hepatic HDL endocytic receptor and deficiency of HDL docking receptor. The latter is associated with and, in part, mediated by downregulation of PDZK1. Together, these abnormalities can increase catabolism and diminish recycling of HDL and contribute to the defective reverse cholesterol/ lipid transport in NS.
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Authors | Nosratola D Vaziri, Pavan Gollapudi, Seungyeup Han, Guity Farahmand, Jun Yuan, Ardeshir Rahimi, Hamid Moradi |
Journal | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
(Nephrol Dial Transplant)
Vol. 26
Issue 10
Pg. 3118-23
(Oct 2011)
ISSN: 1460-2385 [Electronic] England |
PMID | 21459782
(Publication Type: Journal Article)
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Chemical References |
- Antimetabolites, Antineoplastic
- CD36 Antigens
- Carrier Proteins
- Cytoskeletal Proteins
- Lipids
- Lipoproteins, HDL
- Pdzk1 protein, rat
- RNA, Messenger
- Puromycin
- Cholesterol
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Topics |
- Animals
- Antimetabolites, Antineoplastic
(toxicity)
- Blotting, Western
- CD36 Antigens
(genetics, metabolism)
- Carrier Proteins
(genetics, metabolism)
- Cholesterol
(metabolism)
- Cytoskeletal Proteins
- Down-Regulation
- Hypercholesterolemia
(etiology)
- Immunoenzyme Techniques
- Lipids
(analysis)
- Lipoproteins, HDL
(metabolism)
- Liver
(metabolism)
- Male
- Nephrotic Syndrome
(chemically induced, metabolism, pathology)
- Proteinuria
(etiology)
- Puromycin
(toxicity)
- RNA, Messenger
(genetics)
- Rats
- Rats, Sprague-Dawley
- Real-Time Polymerase Chain Reaction
- Up-Regulation
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