Dual-function of triptriolide in podocytes injury: inhibiting of apoptosis and restoring of survival.

Triptriolide (T11) is a natural diterpene diepoxide that derived from Chinese traditional herb medicine (TCHM) Tripterygium wilfordii Hook.F (TWHF). From a structural point of view, T11 is very similar to triptolide (T9), one of the most effectively compounds in TWHF that have already been systematically investigated in the past decades. However, the basic functions and medicinal properties of T11 have not yet been well investigated mainly due to its low abundance in its plant organ. The present study aimed to investigate the protective effects of T11 on puromycin aminonucleoside (PAN) induced apoptotic mouse podocytes and the underlying mechanism. The results showed that T11 had no significant toxicity in podocytes in high dosage, and showed prominent protective effects on PAN induced podocytes injury. Further studies indicated that T11 might exert its protective effects by inhibiting of apoptosis and restoring of survival in PAN induced podocytes.

Sialic acid attenuates puromycin aminonucleoside-induced desialylation and oxidative stress in human podocytes.

Sialoglycoproteins make a significant contribution to the negative charge of the glomerular anionic glycocalyx-crucial for efficient functioning of the glomerular permselective barrier. Defects in sialylation have serious consequences on podocyte function leading to the development of proteinuria. The aim of the current study was to investigate potential mechanisms underlying puromycin aminonucleosisde (PAN)-induced desialylation and to ascertain whether they could be corrected by administration of free sialic acid. PAN treatment of podocytes resulted in a loss of sialic acid from podocyte proteins. This was accompanied by a reduction, in the expression of sialyltransferases and a decrease in the key enzyme of sialic acid biosynthesis N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). PAN treatment also attenuated expression of the antioxidant enzyme superoxide dismutase (mSOD) and concomitantly increased the generation of superoxide anions. Sialic acid supplementation rescued podocyte protein sialylation and partially restored expression of sialyltransferases. Sialic acid also restored mSOD mRNA expression and quenched the oxidative burst. These data suggest that PAN-induced aberrant sialylation occurs as a result of modulation of enzymes involved sialic acid metabolism some of which are affected by oxidative stress. These data suggest that sialic acid therapy not only reinstates functionally important negative charge but also acts a source of antioxidant activity.

Effect of dietary antioxidants on puromycin aminonucleoside nephrotic syndrome.

Several studies indicate the pathophysiological importance of reactive oxygen species in rats with nephrotic syndrome induced by puromycin aminonucleoside, an experimental model of the human minimal change disease. The role of reactive oxygen species in these rats was further evaluated, examining the effect of dietary deficiency and supplementation of antioxidants (vitamin E and selenium) on biochemical and renal ultrastructural alterations induced by puromycin aminonucleoside. Male Wistar rats, weaned at 3 weeks, were placed on diets normal, deficient or supplemented in vitamin E and selenium for 4 weeks. At the end of this period, rats were divided in two groups: control (sacrificed without any further treatment) and nephrotic (injected with puromycin aminonucleoside and sacrificed 7 and 22 days later). In control rats, the dietary deficiency or supplementation of antioxidants resulted in no significative differences in renal function, proteinuria or kidney ultrastructure. However, kidney lipoperoxidation, kidney glutathione peroxidase activity and circulating levels of vitamin E changed according to the amount of antioxidants in the diet. Seven days after the injection of puromycin aminonucleoside, rats fed normal, deficient or supplemented diets, developed nephrotic syndrome. However, proteinuria, hypoproteinemia, renal dysfunction and ultrastructural alterations were higher in rats fed a deficient diet. In contrast, proteinuria and kidney ultrastructural alterations were lower in rats fed a supplemented diet. Kidney lipoperoxidation and glutathione peroxidase activity increased on day 7 in rats fed a normal or a deficient diet, but not in rats fed a supplemented diet. This study shows that nephrotic syndrome induced by puromycin aminonucleoside in rats is modified by dietary antioxidants (vitamin E and selenium). Dietary supplementation ameliorates it and dietary deficiency exacerbates it.(ABSTRACT TRUNCATED AT 250 WORDS)