1. Cytotoxic selectivity and apoptosis induction of piericidin A contributes potentially to its insecticidal effect against Mythimna separata (Lepidoptera: Noctuidae) larvae
Shaorong Luan, Solange Muhayimana, Qiqi Zhu, Qingchun Huang, Xianfei Zhang, Jiuyong Xu, Hui Xiong Pestic Biochem Physiol . 2019 Jun;157:19-25. doi: 10.1016/j.pestbp.2019.03.002.
Piericidin A (PIA), an active inhibitor of Complex I, is widely used in studies of the anti-bacterial and anti-disease competence, but its physiological and mechanistic effects have rarely been clearly defined in insect individual or insect cells. The present study reveals the considerable insecticidal activity of PIA on Mythimna separata larvae by using a comparison with Aphis craccivora adult, and the cytotoxic selectivity induced by PIA on lepidopteran Tn5B1-4 cells. We demonstrate that the viability of Tn5B1-4 cells is inhibited by PIA in a time- and concentration-dependent manner with IC50value of 0.061 μM, whilst PIA shows slight inhibitory effect on the viability of HepG2 and Hek293 cells with IC50value of 233.97 and 228.96 μM, respectively. The inhibitory effect of PIA on the proliferation of Tn5B1-4 cells is significant and persistent, causing a series of morphological changes including cell shrinkage, condensed and fragmented nuclei. Intracellular biochemical assays show that PIA induces apoptosis of Tn5B1-4 cells coincides with a decrease in the mitochondrial membrane potential. PIA in Tn5B1-4 cells can be chelated by EDTA, thereby losing cytotoxicity, whereas exogenous Ca2+restores the cytotoxicity of PIA by chelating with EDTA in a competitive manner. Our findings highlight the importance of the long-lasting cytotoxicity and the cytoxic selectivity on Tn5B1-4 cells caused by PIA, which ensure the identification of insecticidal effect of PIA against insect pests.
2. Non-haem iron and the dissociation of piericidin A sensitivity from site 1 energy conservation in mitochondria from Torulopsis utilis
R A Clegg, P B Garland Biochem J . 1971 Aug;124(1):135-51. doi: 10.1042/bj1240135.
1. The aerobic incubation of iron-deficient Torulopsis utilis cells for 12h under non-growing conditions results in the recovery by mitochondria of the previously absent site 1 energy conservation and sensitivity to piericidin A. 2. The recovery of piericidin A sensitivity but not site 1 is prevented by the presence of cycloheximide (100mug/ml) in the medium used for aerobic incubation of the cells. Rotenone sensitivity behaved similarly. 3. Chloramphenicol, erythromycin and tetracycline were without effect on the recovery of site 1 and piericidin A sensitivity. 4. Inclusion of (59)Fe in the growth medium can be used as the basis for a highly sensitive assay for non-haem iron. 5. Iron-limited growth of T. utilis lowers the concentration of both non-haem iron and acid-labile sulphide of submitochondrial particles by over 20-fold compared with the ;normal' situation with iron-supplemented glycerol-limited growth. 6. Increases in the non-haem iron and acid-labile sulphide concentrations of submitochondrial particles occur when site 1 and piericidin A sensitivity are recovered. The increase is approximately halved by the presence of cycloheximide. 7. The non-haem iron of T. utilis submitochondrial particles does not exchange with added iron. 8. Continuous culture of T. utilis at the transition between glycerol- and iron-limitation results in cells where mitochondria possess site 1 energy conservation but lack piericidin A sensitivity. 8. It is concluded, in contrast with widely held views to the opposite, that energy conservation at site 1 does not require electron flow to proceed through a piericidin A- or rotenone-sensitive route. 9. Restriction of the iron supplied to growing T. utilis to a concentration just above that required for growth limitation demonstrates that a 10- to 20-fold decrease of the ;normal' non-haem iron concentration of both cells and mitochondria is without effect on the growth yield per unit of carbon source. Submitochondrial particles prepared from such iron-restricted but otherwise functionally normal cells have a non-haem iron concentration of about 0.5-0.8ng-atom/mg of protein. It is concluded that the concentration of iron-sulphur protein required for normal function by the respiratory chain is close to the concentrations of cytochromes and flavoproteins.
3. New piericidin glucosides, glucopiericidins A and B
R Kawahara, K Nagaoka, K Mogi, S Ishizeki, M Matsumoto, T Nakashima J Antibiot (Tokyo) . 1987 Feb;40(2):149-56. doi: 10.7164/antibiotics.40.149.
The new piericidin group antibiotics, glucopiericidins A and B were isolated from the culture broth of Streptomyces pactum S48727 (FERM P-8117) as co-metabolite of piericidin A1. The structures of glucopiericidins A and B were determined as piericidin A1, 10-O-beta-D-glucoside and piericidin A1, 3'-O-D-glucoside on the basis of their spectral and chemical properties, respectively. Glucopiericidins were more potent in inhibiting antibody formation than piericidin A1 in vitro. In addition, these substances showed better antimicrobial activities than piericidin A1. Acute toxicities of these substances in mice were lower than that of piericidin A1. This indicates that D-glucose in glucopiericidin molecules is important in modulating their physiological activities.