Tyrosine catabolism enhances genotoxic chemotherapy by suppressing translesion DNA synthesis in epithelial ovarian cancer.

Amino acid metabolism has been actively investigated as a potential target for antitumor therapy, but how it may alter the response to genotoxic chemotherapy remains largely unknown. Here, we report that the depletion of fumarylacetoacetate hydrolase (FAH), an enzyme that catalyzes the final step of tyrosine catabolism, reduced chemosensitivity in epithelial ovarian cancer (EOC). The expression level of FAH correlated significantly with chemotherapy efficacy in patients with EOC. Mechanistically, under genotoxic chemotherapy, FAH is oxidized at Met308 and translocates to the nucleus, where FAH-mediated tyrosine catabolism predominantly supplies fumarate. FAH-produced fumarate binds directly to REV1, resulting in the suppression of translesion DNA synthesis (TLS) and improved chemosensitivity. Furthermore, in vivo tyrosine supplementation improves sensitivity to genotoxic chemotherapeutics and reduces the occurrence of therapy resistance. Our findings reveal a unique role for tyrosine-derived fumarate in the regulation of TLS and may be exploited to improve genotoxic chemotherapy through dietary tyrosine supplementation.

Impacts of underwater topography on the distribution of microplastics in lakes: A case from Dianchi Lake, China.

The spatial distribution of microplastics and the factors influencing their distribution in lakes are important aspects of plastics pollution studies. This study investigated the impacts of lake underwater topography on the spatial distribution of microplastics in Dianchi Lake in China. Data on spatial distribution of microplastics were obtained by pump sampling, microscopic examination, and polymer identification. Parameters of underwater topography were extracted from an isobaths map of Dianchi Lake. The relationships between underwater topography and the abundance of microplastics were analyzed. The results showed that for the northern part of the lake, water depth, slope gradient, relief, roughness and surface curvature have significant relationships with the spatial distribution of microplastics. In the southern part, only roughness showed a significant relationship. The roughness is the only important factor which impacts the microplastics distribution in both parts of the lake and the whole lake. These differences between the northern part and the southern part of the lake are related to the stronger circular currents in the southern part of the lake. These results showed that the impacts of underwater topography manifest themselves well when lake currents are weak, and these impacts are reduced or muted when lake currents are strong. Our research results provide a good reference for understanding distribution and migration principle of microplastics in lakes.

Influence of ofloxacin on photosystems I and II activities of Microcystis aeruginosa and the potential role of cyclic electron flow.

Pollution with antibiotics poses a great risk to aquatic ecosystems. Although some toxic effects of antibiotics on photosystem II (PSII) have been documented, their toxicity to photosystem I (PSI) is still unclear. In this study, effects of ofloxacin on activities of both PSI and PSII of Microcystis aeruginosa (Kützing) Kützing were investigated. Exposure to 0.1 mg L(-)(1) ofloxacin led to increases in contents of chlorophyll a and carotenoids and photosynthetic activity of M. aeruginosa. PSI activity and its electron transport were not affected by 0.1 mg L(-)(1) ofloxacin. When M. aeruginosa was exposed to ≥10 mg L(-)(1) ofloxacin, the electron transport rates of PSI and PSII, the yield of cyclic electron flow (CEF) and the contribution of linear electron flow (LEF) to PSI decreased whereas Y(NA) (limitation of donor side of PSI) and Y(NO) (the quantum yield of non-regulated energy dissipation in PSII) significantly increased. CEF had a significant contribution to alleviating the inhibitory effect of ofloxacin on PSI of M. aeruginosa treated with low concentrations of ofloxacin. The protective role CEF for tolerance of PSI to the toxicity of ofloxacin decreased with increasing ofloxacin concentration.

Herbicidal effects of harmaline from Peganum harmala on photosynthesis of Chlorella pyrenoidosa: probed by chlorophyll fluorescence and thermoluminescence.

The herbicidal effects of harmaline extracted from Peganum harmala seed on cell growth and photosynthesis of green algae Chlorella pyrenoidosa were investigated using chlorophyll a fluorescence and thermoluminescence techniques. Exposure to harmaline inhibited cell growth, pigments contents and oxygen evolution of C. pyrenoidosa. Oxygen evolution was more sensitive to harmaline toxicity than cell growth or the whole photosystem II (PSII) activity, maybe it was the first target site of harmaline. The JIP-test parameters showed that harmaline inhibited the donor side of PSII. Harmaline decreased photochemical efficiency and electron transport flow of PSII but increased the energy dissipation. The charge recombination was also affected by harmaline. Amplitude of the fast phase decreased and the slow phase increased at the highest level of harmaline. Electron transfer from QA(-) to QB was inhibited and backward electron transport flow from QA(-) to oxygen evolution complex was enhanced at 10 µg mL(-1) harmaline. Exposure to 10 µg mL(-1) harmaline caused appearance of C band in thermoluminescence. Exposure to 5 µg mL(-1) harmaline inhibited the formation of proton gradient. The highest concentration of harmaline treatment inhibited S3QB(-) charge recombination but promoted formation of QA(-)YD(+) charge pairs. P. harmala harmaline may be a promising herbicide because of its inhibition of cell growth, pigments synthesis, oxygen evolution and PSII activities.

Cu(2+) inhibits photosystem II activities but enhances photosystem I quantum yield of Microcystis aeruginosa.

Responses of photosystem I and II activities of Microcystis aeruginosa to various concentrations of Cu(2+) were simultaneously examined using a Dual-PAM-100 fluorometer. Cell growth and contents of chlorophyll a were significantly inhibited by Cu(2+). Photosystem II activity [Y(II)] and electron transport [rETRmax(II)] were significantly altered by Cu(2+). The quantum yield of photosystem II [Y(II)] decreased by 29 % at 100 µg L(-1) Cu(2+) compared to control. On the contrary, photosystem I was stable under Cu(2+) stress and showed an obvious increase of quantum yield [Y(I)] and electron transport [rETRmax(I)] due to activation of cyclic electron flow (CEF). Yield of cyclic electron flow [Y(CEF)] was enhanced by 17 % at 100 µg L(-1) Cu(2+) compared to control. The contribution of linear electron flow to photosystem I [Y(II)/Y(I)] decreased with increasing Cu(2+) concentration. Yield of cyclic electron flow [Y(CEF)] was negatively correlated with the maximal photosystem II photochemical efficiency (F v/F m). In summary, photosystem II was the major target sites of toxicity of Cu(2+), while photosystem I activity was enhanced under Cu(2+) stress.

Excess Ca(2+) does not alleviate but increases the toxicity of Hg(2+) to photosystem II in Synechocystis sp. (Cyanophyta).

This study demonstrated that excess Ca(2+) increased the toxicity of Hg(2+) to PSII of cyanobacterium Synechocystis sp. using fast rise chlorophyll fluorescence test. Excess Ca(2+) increased the inhibitory effect of Hg(2+) on O2 evolution. Exposure to Hg(2+) caused increase in functional antenna size (ABS/RC), trapping rate of reaction center (TR0/RC), dissipated energy flux per reaction center (DI0/RC) and maximum quantum yield of non-photochemical deexcitation ( [Formula: see text] ), indicating that some reaction centers were transformed to dissipation sinks under Hg(2+) stress. Hg(2+) stress slowed down electron transport on both donor side and acceptor side and caused accumulation of P680(+). Excess Ca(2+) intensified all the Hg(2+) toxic effects on PSII function and led to dysfunction of PSII. The number of reaction centers that were transformed into dissipation sinks increased with increasing Ca(2+) concentration.

Toxic effects of mercury on PSI and PSII activities, membrane potential and transthylakoid proton gradient in Microsorium pteropus.

Mercury (Hg) is one of the top toxic metals in environment and it poses a great risk to organisms. This study aimed to elucidate the toxic effects of Hg(2+) on energy conversion of photosystem I (PSI) and photosystem II (PSII), membrane potential and proton gradient of Microsorium pteropus (an aquatic plant species). Contents of chlorophyll a, chlorophyll b and carotenoids, quantum yield and electron transfer of PSI and PSII of M. pteropus exposed to various concentrations of Hg(2+) were measured. With increasing Hg(2+) concentration, quantum yield and electron transport of PSI [Y(I) and ETR(I)] and PSII [Y(II) and ETR(II)] decreased whereas limitation of donor side of PSI [Y(ND)] increased. At ⩾165µgL(-1) Hg(2+), quantum yield of non-light-induced non-photochemical fluorescence quenching in PSII [Y(NO)] significantly increased but quantum yield of light-induced non-photochemical fluorescence quenching [Y(NPQ)] decreased. Membrane potential (Δψ) and proton gradient (ΔpH) of M. pteropus were reduced significantly at 330µg L(-1) Hg(2+) compared to control. Mercury exposure affected multiple sites in PSII and PSI of M. pteropus.

EFFECT OF CHROMIUM(VI) ON PHOTOSYSTEM II ACTIVITY AND HETEROGENEITY OF SYNECHOCYSTIS SP. (CYANOPHYTA): STUDIED WITH IN VIVO CHLOROPHYLL FLUORESCENCE TESTS(1).

The inhibitory effect of Cr(VI) on the PSII of Synechocystis sp. was studied. Cr(VI) reduced O2 evolution and inhibited the water-splitting system in PSII. S-states test and flash induction test showed that Cr(VI) exposure increased the proportion of inactivated PSII (PSIIX ) and PSIIß reaction centers, which increased the fluxes of dissipated energy. JIP test and QA (-) reoxidation test demonstrated that Cr(VI) treatment induces inhibition of electron transport from QA (-) to QB /QB (-) and accumulation of P680 (+) . More QA (-) had to be oxidized through S2 (QA QB )(-) charge recombination and oxidation by PQ9 molecules in PSII under Cr(VI) stress. These changes finally decreased the index of photosynthesis performance.

Toxic effects of amoxicillin on the photosystem II of Synechocystis sp. characterized by a variety of in vivo chlorophyll fluorescence tests.

Amoxicillin is one of the widely used antibiotics of environmental concern. This study shows that amoxicillin has toxic effects on the photosynthesis of Synechocystis sp. Its inhibitory effects on photosystem II (PSII) of Synechocystis sp. were investigated by using a variety of in vivo chlorophyll fluorescence tests. The inhibitory effects of amoxicillin on PSII activity of Synechocystis sp. are concentration-dependent. Amoxicillin exposure leads to slowing down of electron transport on both donor side and acceptor side and causes accumulation of P680(+). Q(A)(-) reoxidation test revealed that amoxicillin hinders electron transfer from Q(A)(-) to Q(B)/Q(B)(-) and more Q(A)(-) is oxidized through S(2)(Q(A)Q(B))(-) charge recombination. Analysis of PSII heterogeneity demonstrated that an exposure to amoxicillin increases the proportion of inactive PSII (PSII(X)) centers and the proportion of PSII centers with small antenna (PSIIbeta). These changes finally result in deterioration of full photosynthesis performance.