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Alterations in renal cytosolic phospholipase A 2 and cyclooxygenases in polycystic kidney disease
Author(s) -
Aukema Harold M.,
Adolphe Jennifer,
Mishra Suparna,
Jiang Jieyuan,
Cuozzo Francis P.,
Ogborn Malcolm R.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0460fje
Subject(s) - endocrinology , polycystic kidney disease , medicine , phospholipase a2 , kidney , cyclooxygenase , enzyme , cytosol , kidney disease , phospholipase , eicosanoid , renal function , chemistry , biology , arachidonic acid , biochemistry
Cytosolic phospholipase A 2 (cPLA 2 ), cyclooxygenase‐1 (COX‐1), and cyclooxygenase‐2 (COX‐2) regulate the formation of physiologically active prostaglandins, the production of which is known to be elevated in several renal disorders. We studied the relevance of these enzymes in polycystic kidney disease (PKD) by using two models of the disease: a model in which decline in renal function begins in adulthood (CD1‐ pcy/pcy mouse) and one in which it occurs early, during growth (Han:SPRD‐cy rat). Immunoblotting analyses of cytosolic and particulate kidney fractions revealed that cPLA 2 levels are significantly higher (by 34–131%) in the latter stages of the disease in both models. Renal COX enzymes were found only in the particulate fractions, with COX‐1 87% higher in 6‐month‐old CD1‐ pcy/pcy mice compared with normal controls, and 110% higher in male 70‐day‐old Han:SPRD‐ cy rats with cystic kidneys compared with controls. Renal COX‐2 was detected only in the rats and was 58% lower in diseased kidneys of 70‐day‐old male Han:SPRD‐ cy rats, indicating that cPLA 2 is coupled to COX‐1 in the kidney. The altered levels of these eicosanoid‐regulating enzymes has implications for the use of NSAIDS and specific COX inhibitors in individuals with this disorder.