Polarized distribution of oxalate transport systems in LLC-PK1 cells, a line of renal epithelial cells

Abstract

Although oxalate is a major component of kidney stones, the factors affecting renal oxalate handling are poorly understood. This uncertainty stems in part from complexities inherent to available preparations; thus the present studies examined oxalate handling in a simpler model system, LLC-PK1 cells, an epithelial cell line of porcine origin. Initial studies on monolayers in dishes demonstrated that these cells accumulate oxalate via a process or processes sensitive to the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Subsequent studies using LLC-PK1 monolayers on membrane filters examined the characteristics and distribution of these transporter(s). At the apical surface, DIDS-sensitive uptake was sensitive to [Cl-] but not [SO4(2-)] or [HCO3-] and was unaffected by alterations in pH or membrane potential. At the basolateral surface, oxalate uptake was [Cl-] insensitive but markedly affected by variation in pH, [SO4(2-)], or [HCO3-]. Uptake at the two membrane surfaces was also differentially affected by transport inhibitors and organic acids. Thus LLC-PK1 cells appear to express unique transporters at each membrane surface: oxalate/Cl- exchange at the apical surface and oxalate/SO4(2-) (or HCO3-) exchange at the basolateral surface.

Calcium Oxalate Deposition in Renal Cell Carcinoma Associated With Acquired Cystic Kidney Disease

“…It may be mitogenic at lower concentration but may cause cell necrosis or apoptosis at higher concentration. 20,30 CaOx can induce intracellular formation of reactive oxygen species and inhibit several cytosolic enzymes, which may account for its cytotoxic effects. 20,30 CaOx is the major factor in renal tissue injury in renal oxalosis, a condition characterized by renal tissue deposition of CaOx.…”

“…20,30 CaOx can induce intracellular formation of reactive oxygen species and inhibit several cytosolic enzymes, which may account for its cytotoxic effects. 20,30 CaOx is the major factor in renal tissue injury in renal oxalosis, a condition characterized by renal tissue deposition of CaOx. In the context of ESRD, CaOx was thought to promote cyst and tumor formation through both mechanical obstructions of renal tubules and regulation of tubular cell cycles.…”

Oxalate: From the Environment to Kidney Stones

“…Evidence for oxalate transport across both cell membrane domains came from in vitro experiments with LLC-PK1 cells. In this experimental model, oxalate secretion was presented by a two step process; the uptake of oxalate occured in exchange for SO 4 2-or HCO 3 -across the proximal tubule cell BLM, followed by a release of oxalate in exchange for SO 4 2-or Cl -across the BBM (147). In rabbit renal BBM, both Na + -dependent and Na + -independent modes of oxalate transport were demonstrated, whereas the Na + -driven mode was almost negligible (148).…”

Oxalate upregulates expression of IL-2Rβ and activates IL-2R signaling in HK-2 cells, a line of human renal epithelial cells

“…The formation of calcium oxalate stones in the kidney is the most common pathological condition involving oxalate. Oxalate is a metabolic end product, which is filtered at the glomerulus and undergoes bidirectional transport in the renal tubules before being excreted by the kidney (13,14,24). In addition to kidney stones, oxalate deposits are associated with renal cysts in acquired renal cystic disease, benign neoplasms of the breast, and hyperplastic thyroid glands, among others (7,10,28,34).…”