Renal gangliosides are involved in lead intoxication

Abstract

The biological effects of lead are well defined; however, neither the risk exposure level nor the subcellular mechanism of its action is completely clear. The present work was undertaken to investigate the effects of low level and long term lead exposure on the composition and expression of rat renal gangliosides. In order to identify ganglioside expression, frozen sections of kidneys were stained with monoclonal antibodies GMB16 (GM1 specific), GM28 (GM2 specific), AMR-10 (GM4 specific) and CDW 60 (9-O-Ac-GD3 specific). Strong reactivity was observed for GMB28, AMR-10 and CDW 60, while GMB16 developed only weak labelling in treated kidney compared with the control. The alterations in the expression of renal gangliosides observed by immunohistochemistry were accompanied by quantitative and qualitative changes in the thin layer chromatography of total gangliosides isolated from kidney tissues. Lead treatment produced a significant increase in 9-O-Ac GD3, a ganglioside involved in apoptotic processes. In agreement with this result, a significant decrease in the number of apoptotic glomerular cells was observed with the TUNEL assay. These findings lead us to suggest that alterations in renal gangliosides produced by low level lead exposure are associated with the apoptotic processes that take place in the kidney. These findings provide evidence that low level and long term lead exposure produces renal ganglioside alterations with urinary microalbumin excretion. The results suggest that lead levels within the limits of biological tolerance already cause molecular renal damage without clinical signs of toxicity.

Podocyte Pathology and Nephropathy – Sphingolipids in Glomerular Diseases

“…A similar pathway has been recently described in TNFα-mediated apoptosis (62, 63). Significant 9- O -acetyl GD3 accumulation, together with increases in GM2 and GM4 gangliosides in glomerular cells was also observed after low level and long term lead exposure and was associated with decreased apoptosis in glomerular cells suggesting that GD3-O acetylation could represent a new strategy to attenuate apoptosis in renal glomerular cells and contribute to cell survival as observed during lead exposure (64). …”

Hepatic fibrogenesis and transforming growth factor/Smad signaling activation in rats chronically exposed to low doses of lead

“…BAT was defined as the maximum permissible quantity of a chemical substance or its metabolites or the maximum permissible deviation from the norm of biological parameters induced by lead in exposed humans. (Drexler et al, 2008;Pérez Aguilar et al, 2008). The controls received ordinary tap water throughout the experimental period.…”

“…Lead is a nonessential toxic metal whose widespread use has caused extensive environmental contamination and health problems such as cognitive and behavioral impairment, anemia, gastrointestinal toxicity and chronic renal failure (Ademuyiwa et al, 2007;Lanphear et al, 2005;Patrick, 2006;Pérez Aguilar et al, 2008;Villeda-Hernandez et al, 2001). There is growing evidence that levels of lead intake considered innocuous a few years ago could result in subtle noxious effects in both humans and experimental animals (Gilbert and Weiss, 2006;Park et al, 2006;Spivey, 2007).…”

Gangliosides in Podocyte Biology and Disease

“…GD3 O-acetylation has been related to viral infection and to the resistance to apoptosis of tumor cells [24]. Moreover, 9-O-acetyl-GD3 has been found specifically increased in rat kidney in response to lead exposure, which produces microalbuminuria [25].…”