Is the Increase in Renal Papillary Phospholipid Biosynthesis a Protective Mechanism against Injury?

Abstract

Mercuric chloride (HgCl₂) is a well-known renal toxic that causes acute renal failure. The effect of HgCl₂ treatment and the protection by thyroxine were studied in rat renal papilla (P), outer medullary inner stripe (OMIS), outer medullary outer stripe (OMOS) and cortical phospholipids (PhLs). HgCl₂ brought about an increase in the total phospholipid content in P and OMIS but a drop in OMOS and cortex. Only phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) accounted for such changes. Thyroxine, injected on HgCl₂-treated rats, partially reversed the effect of the toxic metal in P and OMIS while completely reversed the PtdCho drop in OMOS and cortex. However, the hormone failed to recover the sphingomyelin increase in P, the PtdEtn shortage in OMIS, OMOS and partially reversed the drop in the cortex. When thyroxine was injected whith-out toxic treatment, no effect was observed in the phospholipid content of any kidney zone. Results obtained by using ³²P as a precursor to study the PhL de novo synthesis were consistent with those of the phospholipid content. Thus, a radioactivity increase – associated with PtdCho and PtdEtn – was observed in the kidney zones where said endogenous PhLs had risen. But in OMOS and cortex, where PtdCho and PtdEtn had dropped, they were also accompanied by a decrease in radioactivity. The thyroxine-induced recovery phase also paralleled the phospholipid content results with those of the de novo synthesis. We suggest that the decrease in the renal phospholipid de novo synthesis may constitute one biochemical explanation of the selective renal toxic effect exerted by HgCl₂ and that the increase observed in the renal phospholipid metabolism – induced by the toxic treatment in OMIS and P – may represent a protective mechanism of these zones against toxic injury. Moreover, recovery promoted by thyroxine treatment in OMOS and cortex was accompanied by the reversion of the corresponding PtdCho decrease induced by HgCl₂.

Environmental hyperosmolality regulates phospholipid biosynthesis in the renal epithelial cell line MDCK

“…For propidium iodide staining, the fi xed cells were washed once with PBS and from our laboratory demonstrated that the inner renal medulla has the most-active phospholipid synthesis and membrane turnover of all kidney zones ( 24 ). We have demonstrated that the ability of the inner renal medulla to renew the phospholipidic constituents of cell membranes is a defense mechanism against diverse injuries (25)(26)(27). We have speculated that such an active phospholipid metabolism in renal medullary cells is a consequence of the high interstitial osmolality, but we did not confi rm this hypothesis.…”

High Glucose Concentrations Stimulate Renal Papillary Phosphatidylcholine Biosynthesis

“…Consequently, this increase in biosynthesis might be a reflection of phospholipid renewal. We propose that such a renewal of phospholipids represents a protective mechanism to preserve membrane homeostasis in the face of a metabolic insult, as we have previously shown for a model of acute renal failure [7]. …”

“…For each experiment, 5 mg of tissue slices (0.5 mm thick) from control or diabetic rats were collected in 0.25 ml of 10 m M Tris/HCl solution (pH 7.4) containing electrolytes and 5 m M glucose [7]. Samples were incubated at 37°C with 14 mCi of [ 32 P]-sodium orthophosphate in a metabolic shaking bath, as described previously [7]. …”

“…Under physiological conditions, where no changes in phospholipid mass occur, phospholipid de novo synthesis offsets the amount of degraded molecules in order to maintain biomembrane integrity. This phospholipid renewal is a protective and specific process that cells use to avoid membrane injury [7]. In a model of acute renal failure induced by mercuric chloride, we demonstrated that papillary cells preclude the deleterious effects of the toxin by increasing their phospholipid turnover, while medullary and cortical cells, that are not efficient enough to renew their phospholipids, undergo necrosis [7].…”

“…This phospholipid renewal is a protective and specific process that cells use to avoid membrane injury [7]. In a model of acute renal failure induced by mercuric chloride, we demonstrated that papillary cells preclude the deleterious effects of the toxin by increasing their phospholipid turnover, while medullary and cortical cells, that are not efficient enough to renew their phospholipids, undergo necrosis [7]. In contrast, nephrotoxins such as aminoglycosides have been reported to induce phospholipid accumulation.…”