Cytochalasin A

Biological herbicides have received much attention due to their abundant resources, low development cost, unique targets and environmental friendliness. This study reveals some interesting effects of mycotoxin cytochalasin A (CA) on photosystem II (PSII). Our results suggested that CA causes leaf lesions onAgeratina adenophoradue to its multiple effects on PSII. At a half-inhibitory concentration of 58.5 μΜ (I50, 58.5 μΜ), the rate of O2evolution of PSII was significantly inhibited by CA. This indicates that CA possesses excellent phytotoxicity and exhibits potential herbicidal activity. Based on the increase in the J-step of the chlorophyll fluorescence rise OJIP curve and the analysis of some JIP-test parameters, similar to the classical herbicide diuron, CA interrupted PSII electron transfer beyond QAat the acceptor side, leading to damage to the PSII antenna structure and inactivation of reaction centers. Molecular docking model of CA and D1 protein ofA. adenophorafurther suggests that CA directly targets the QBsite of D1 protein. The potential hydrogen bonds are formed between CA and residues D1-His215, D1-Ala263 and D1-Ser264, respectively. The binding of CA to residue D1-Ala263 is novel. Thus, CA is a new natural PSII inhibitor. These results clarify the mode of action of CA in photosynthesis, providing valuable information and potential implications for the design of novel bioherbicides.

Cytochalasin A at 10-20 mug/ml inhibits growth and sugar uptake by Saccharomyces strain 1016. The effects of cytochalasin A in intact cells were completely prevented when 1 mM cysteine or dithiothreitol was added along with cytochalasin A, but were not eliminated by thiols added after inhibition had occurred. Purified yeast hexokinase, glucose-6-P dehydrogenase, phosphofructokinase and aldolase were not sensitive to cytochalasin A (20 mug/ml). Glyceraldehyde-3-P dehydrogenase was strongly inhibited by cytochalasin A (5 mug/ml); activity was promptly restored by thiols. Anaerobic glycolysis was inhibited by cytochalasin A or by iodoacetate; unlike iodoacetate, cytochalasin A did not cause accumulation of sugar phosphates. In contrast, cytochalasin A, but not iodoacetate, inhibited isolated membrane-bound ATPases. Cytochalasin A is a sulfhydryl-reactive agent and has membrane-related effects (adenosine triphosphatase) which may well be the basis of its interference with energy-dependent uptake of solutes.

Cytochalasin B (CB) has been shown to be a potent depressant of the antigen-induced clone expansion and terminal differentiation of mouse B-lymphocytes to antibody-forming cells. This effect could be the result of the microfilament-disrupting effect of CB with subsequent inhibition of antigen-sIg complex redistribution, a series of events which seems to be necessary for B-lymphocyte activation. CB is not very active in depressing capping and will inhibit glucose transport. To further investigate the mechanism of action of cytochalasins, the effect of cytochalasin A (CA) on cap formation and plaque-forming cell generation was studied, since CA is less inhibitory of glucose transport and more inhibitory of cap formation. The results presented here indicate that complexes of anti-Ig-sIg will be prevented from capping by as little as 1 microgram of CA, a quantity sufficient to depress markedly the generation of plaque-forming cells to SRBC in culture. These results further confirm our conclusion that the depression of B-lymphocyte activation may be related to the depression of cap formation. It also strongly suggested that inhibition of glucose transport can be regraded as a negligible factor in this depression.