Phosmet induces up-regulation of surface levels of the cellular prion protein

Abstract

Chronic (2 day) exposure of human neuroblastoma cells to the organophosphate pesticide phosmet induced a marked concentration-dependent increase in the levels of PrP present on the cell surface as assessed by biotin labelling and immunoprecipitation. Levels of both phospholipase C (PIPLC)-releasable and non-releasable forms of PrP were increased on the plasma membrane. These increases appear to be due to post-transcriptional mechanisms, since PrP mRNA levels as assessed by Northern blotting were unaffected by phosmet treatment. These data raise the possibility that phosmet exposure could increase the susceptibility to the prion agent by altering the levels of accessible PrP.

Insecticide use: Contexts and ecological consequences

“…The accumulation of pesticide residues in the food chain through the consumption of crabs and fishes from pesticide-sprayed rice paddy fields was thought to be the cause of a musculo-skeletal condition in humans (Krishnamachari and Bhat, 1978;Mohan, 1987), but more recent studies have shown that the disease was the result of a high rate of inbreeding among affected communities (Agarwal et al, 1997). The BSE crisis in the UK was improbably attributed on occasion to OP use (Gordon et al, 1998;Purdey, 1996). The recent decline in vulture populations in India was thought to be pesticide induced (Anon., 1999b;Nair, 1999;Prakash, 1999) until it was found to be the result of an unexpected interaction between a veterinary medicine (diclofenac) and vulnerable avian kidneys (Green et al, 2004;Oaks et al, 2004).…”

BSE did not cause variant CJD: an alternative cause related to post-industrial environmental contamination

“…Mark Purdey has speculated that prion disease could be linked to either organophosphate pollution (14) or imbalances in the metal-ion content of foodstuffs, or a combination of both (15). Certainly organophosphates can increase the expression of PrP c as demonstrated by cell culture experiments (16), and increased PrP c expression shortens the incubation time for prion disease (17). However, it is difficult to determine at present if organophosphates play a part in the aetiology of any prion disease.…”

Ecosystems supporting clusters of sporadic TSEs demonstrate excesses of the radical-generating divalent cation manganese and deficiencies of antioxidant co factors Cu, Se, Fe, Zn

“…A tenfold upregulation of the surface expression of PrP was invoked after Whatley et al introduced 12 ppm doses of phosmet into neuroblastoma cell cultures expressing PrP (155). Such a tenfold upregulation of the cuproprotein PrP 'in vivo' would place further demands upon already depleted supplies of free copper in the neurone, leading to the eventual failure of PrP to maintain its tertiary conformation, plus a failure of PrP to perform its putative role in delivering Cu to the superoxide scavenger, SOD 1 (40).…”