Ziram is a dimethyldithiocarbamate fungicide which can cause intraneuronal calcium (Ca2+) dysregulation and subsequently neuronal death. The signaling mechanisms underlying ziram-induced Ca2+ dyshomeostasis and neurotoxicity are not fully understood. NCX3 is the third isoform of the sodium-calcium exchanger (NCX) family and plays an important role in regulating Ca2+ homeostasis in excitable cells. We previously generated a mouse model deficient for the sodium-calcium exchanger 3 and showed that NCX3 is protective against ischemic damage. In the present study, we aim to examine whether NCX3 exerts a similar role against toxicological injury caused by the pesticide ziram. Our data show baby hamster kidney (BHK) cells stably transfected with NCX3 (BHK-NCX3) are more susceptible to ziram toxicity than cells transfected with the empty vector (BHK-WT). Increased toxicity in BHK-NCX3 was associated with a rapid rise in cytosolic Ca2+ concentration [Ca2+i] induced by ziram. Profound mitochondrial dysfunction and ATP depletion were also observed in BHK-NCX3 cells following treatment with ziram. Lastly, primary dopaminergic neurons lacking NCX3 (NCX3−/−) were less sensitive to ziram neurotoxicity than wildtype control dopaminergic neurons. These results demonstrate that NCX3 genetic deletion protects against ziram-induced neurotoxicity and suggest NCX3 and its downstream molecular pathways as key factors involved in ziram toxicity. Our study identifies new molecular events through which pesticides (e.g. ziram) can lead to pathological features of degenerative diseases such as Parkinson’s disease and indicates new targets to slow down neuronal degeneration.
Summary
The suppressive effect of a black oat, Avena strigosa, breeding line KH1a on Meloidogyne spp. was examined in pot tests and on Meloidogyne incognita in pot and field tests. In pot tests, roots of black oats were examined 42-46 days after inoculation of 500 second-stage juveniles. There were significantly fewer egg masses on the roots of KH1a than on 12 black oat cultivars examined. KH1a was a poor host for four isolates of M. incognita, two isolates of M. arenaria and one isolate of M. javanica, and a non-host for one isolate of M. hapla. The effect of autumn and spring cropping of KH1a on soil nematode density was examined in M. incognita-infested fields. Nematode density after autumn cropping of KH1a was significantly lower than that after susceptible black oat, resulting in significantly lower Pf/Pi in KH1a (0.10 and 0.13) than in susceptible black oat (0.42 and 0.74). Damage indices of the succeeding crop, sweet potato, were significantly lower in KH1a plots than in susceptible black oat plots. In spring cropping, there were significantly fewer soil nematodes in KH1a plots than in susceptible black oat plots 3 weeks after cultivation. In both autumn and spring cropping, there was no significant difference in soil nematode density between KH1a and bare fallow. These results suggested that KH1a is a good alternative to current susceptible cultivars for the management of M. incognita.
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