Renal concentrating defect in mice lacking group IV cytosolic phospholipase A2

Downey P.; Sapirstein A.; O'Leary E.; Sun T.-X.; Brown D.; Bonventre J.V.

Keywords: acid, water, enzyme, membrane, mouse, animals, expression, antibody, plasma, ion, kidney, protein, capacity, cell, loop, calcium, mice, vasoconstrictor, experiment, potassium, agents, tissue, tubule, ability, female, cytoskeleton, drinking, article, deprivation, eating, aquaporin, activity, folding, concentration, aquaporins, controlled, prostaglandin, creatinine, fluorescent, animal, osmolality, knockout, phospholipase, technique, study, 4, 1, 3, priority, vasopressins, of, nonhuman, journal, 2, a, Inbred, Osmolar, cytosol, Mice,, C57BL, 6, a2, arachidonic, Proximal, Henle, Phospholipases, icosanoid, leukotriene, b4, e2, Dinoprostone, c4, concentrating


Eicosanoids regulate various cellular functions that are important in physiological and pathophysiological processes. Arachidonic acid is released from membranes by phospholipase A2 (PLA2) activity. Activated macrophages derived from mice lacking the 85-kDa group IV cytosolic PLA2 (cPLA2) have a markedly reduced release of prostaglandin E2 and leukotrienes B4 and C4. Under basal conditions and after furosemide, urinary prostaglandin E2 excretion is reduced in cPLA2-knockout (cPLA2 -/-) mice. Serum creatinine, Na+, K+, and Ca2+ concentrations, glomerular filtration rate, and fractional excretion of Na+ and K+ are not different in cPLA2 -/- and cPLA2 -/- mice. Maximal urinary concentration is lower in 48-h water-deprived cPLA2 -/- mice compared with cPLA2 +/+ animals (1,934 ± 324 vs. 3,541 ± 251 mmol/kgH2O). Plasma osmolality iis higher (337 ± 5 vs. 319 ± 3 mmol/kgH2O) in cPLA2 -/- mice that lose a greater percentage of their body weight (20 ± 2 vs. 13 ± 1%) compared with cPLA2 +/+ mice after water deprivation. Vasopressin does not correct the concentrating defect. There is progressive reduction in urinary osmolality with age in cPLA2 -/- mice. Membrane-associated aquaporin-1 (AQP1) expression, identified by immunocytochemical techniques, is reduced markedly in proximal tubules of older cPLA2 -/- animals but is normal in thin descending limbs. However, Western blot analysis of kidney cortical samples revealed an equivalent AQP1 signal intensity in cPLA2 +/+ and cPLA2 -/- animals. Young cPLA2 -/- mice have normal proximal tubule AQP1 staining. Collecting duct AQP2, -3, and -4 were normally expressed in the cPLA2 -/- mice. Thus mice lacking cPLA2 develop an age-related defect in renal concentration that may be related to abnormal trafficking and/or folding of AQP1 in the proximal tubule, implicating cPLA2 in these processes.

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Título de la Revista: American Journal Physiology-Renal Physiology
Volumen: 280
Número: 4 49-4
Fecha de publicación: 2001