Rotenone resistance

The control of lice, mites and warbleflies continues to be achieved by the older agents. The selection pressure that caused resistance in cattle ticks and sheep blowfly has not been encountered by these other ectoparasites since their less frequent incidence has required less insecticide/acaricide usage. In addition to the OPs, rotenone (92) (the active principle of derris), an uncoupler of oxidative phosphorylation, continues to be used to combat mange. 

Next to rotenone, the Streptomyces mobaraensis metabolite piericidin (also known as shaoguanmycin B), specifically piericidin Ai (44), is perhaps the most studied NADH—U(i oxidoreductase inhibitor and is commonly used as a pharmacological probe of the role of complex I in the mitochondrial ETC. For example, glucose deprivation causes upregulation of ER chaperone protein GRP78 and induces etoposide resistance in human cancer cells. GRP78 is also known to protect tumor cells from apoptosis induced by topoisomerase inhibitors. " Studies have shown that glucose-deprived etoposide-resistant HT-29 human colon carcinoma cells are uniquely sensitive to piericidin A. ... 

I. Thus when electrons enter the alternative respiratory pathway through the rotenone-insensitive NADH dehydrogenase, the external NADH dehydrogenase, or succinate dehydrogenase (Complex II), and pass to O2 via the cyanide-resistant alternative oxidase, energy is not conserved as ATP but is released as heat. A skunk cabbage can use the heat to melt snow, produce a foul stench, or attract beetles or flies. 

Figure 2 Hypoxia inhibits K+ channels in several 02-sensitive tissues, (a) Whole-ceU patch-clamp experiments show K" " current inhibition in response to hy poxia in rat resistance PASMCs. The complex I ETC blocker rotenone and the Kv blocker 4-aminopyridine (4-AP) also inhibit K" current, (b) Using the current clamp mode, resistance PASMCs depolarize in response to hypoxia. (From Ref. 29.) (c,d,e) Hypoxia inhibits outward K" " current in isolated cells from the NEB, CB, and PC-12 cells. (From Refs. 39,105,106.) Inset Proposed mechanism for HPy featuring the effector portion of the pathway.

Figure 10 The effects of ETC inhibitors and hypoxia on AOS generation and pulmonary vascular resistance are concordant. In the Krebs-albumin-perfused isolated rat lungs, PA pressure reflects pulmonary vascular resistance because flow is held constant. Chemiluminescence, measured by two different methods (luminol and lucigenin enhancement), is decreased (white bars) whereas PA pressure is increased (black bars) in response to both rotenone and antimycin. The complex IV inhibitor cyanide does not lower AOS generation (not shown). (From Ref. 35.)...

Rotenone Resinoid 22 7 5 Moderate resistance-some visual change (discoloration/crazing/ checking) occurs II II... 

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