Light Primes the Thermally Induced Detoxification of Reactive Oxygen Species During Development of Thermotolerance in Arabidopsis.

Reactive oxygen species (ROS) serve as critical signaling mediators in plant adaptation responses to environmental stimuli. ROS biosynthesis and metabolism should be tightly regulated, because they often impose oxidative damage on biological molecules, such as DNA and proteins, and on cellular structures. It is known that at high temperatures, ROS rapidly accumulate in plant tissues. Thus, a quick activation of ROS-scavenging systems is necessary for thermal adaptation. However, it is largely unknown how the thermo-induced ROS-detoxifying capacity is enhanced by environmental factors at the molecular level. Here, we demonstrated that environmental light primes the thermally induced ROS detoxification process for development of thermotolerance in Arabidopsis. While the ROS detoxification capacity was markedly enhanced in light-pre-treated plants at high temperatures, its enhancement was not as evident in dark-pre-treated plants. ASCORBATE PEROXIDASE 2 (APX2) is a representative ROS-scavenging enzyme that is activated under heat stress conditions. It was observed that the thermal induction of the APX2 gene was more prominent in light-pre-treated plants than in dark-pre-treated plants. Notably, the light-gated APX2 gene induction was compromised in Arabidopsis mutants lacking the red light photoreceptor phytochrome B (phyB). Furthermore, exogenous application of the antioxidant ascorbate recovered the heat-sensitive phenotype of the phyB mutant. These observations indicate that light-primed ROS-detoxifying capability is intimately linked with the induction of thermotolerance. We propose that the phyB-mediated light priming of ROS detoxification is a key component of thermotolerant adaptation in plants.

UVA Irradiation Enhances Brusatol-Mediated Inhibition of Melanoma Growth by Downregulation of the Nrf2-Mediated Antioxidant Response.

Brusatol (BR) is a potent inhibitor of Nrf2, a transcription factor that is highly expressed in cancer tissues and confers chemoresistance. UVA-generated reactive oxygen species (ROS) can damage both normal and cancer cells and may be of potential use in phototherapy. In order to provide an alternative method to treat the aggressive melanoma, we sought to investigate whether low-dose UVA with BR is more effective in eliminating melanoma cells than the respective single treatments. We found that BR combined with UVA led to inhibition of A375 melanoma cell proliferation by cell cycle arrest in the G1 phase and triggers cell apoptosis. Furthermore, inhibition of Nrf2 expression attenuated colony formation and tumor development from A375 cells in heterotopic mouse models. In addition, cotreatment of UVA and BR partially suppressed Nrf2 and its downstream target genes such as HO-1 along with the PI3K/AKT pathway. We propose that cotreatment increased ROS-induced cell cycle arrest and cellular apoptosis and inhibits melanoma growth by regulating the AKT-Nrf2 pathway in A375 cells which offers a possible therapeutic intervention strategy for the treatment of human melanoma.

Effect of ultraviolet B (302 nm) irradiation on viability, metabolic and detoxification functions of goat hepatocytes--in vitro study.

The object of the present study was to investigate the effect(s) of UV-B irradiation on the functional integrity, metabolic and detoxifying capacity of the isolated goat hepatocytes. Isolated goat hepatocytes were subjected to UV-B irradiation invitro for 0, 250, 500, 1250, 2500 and 7500 Joules/m2 which correspond to the irradiation time of 0, 1, 2, 5, 10 and 30 min. Cells were then analysed for Viability (Trypan blue exclusion test [TBE], 3-[4,5-dimethylthiozol-2yl]-2,5-diphenyltetrazolium bromide [MTT] assay, Membrane integrity (Lactate dehydrogenase [LDH] leakage, Lipid peroxidation) Detoxification (Ureagenesis, Cytochrome P450 activity [CYP450, Diazepam metabolism] and Glutathione-S-Transferase [GST] activity. The results show that there was no difference in functional, metabolic as well as detoxifying parameters of the hepatocytes when irradiated from 0-1250 Joules/m2, whereas a significant alteration was appreciable in the parameters such as LDH leakage, lipid peroxidation, and CYP450 activity when irradiated beyond 1250 Joules/m2. Our present findings suggest that the biologically compatible and feasible dose of UV-B irradiation for xenotransplantation appears to be 1250 Joules/m2.

[Changes in the drug-metabolizing function of the liver in chronic exposure of the body to low doses of ionizing radiation]. / Izmenenie farmakometaboliziruiushchei funktsii pecheni pri khronicheskom vozdeistvii na organizm malykh doz ioniziruiushchego izlucheniia.

When receiving sanatory treatment in Odessa persons residing at the areas with strict radioecological control (Chernigov, Zhitomir, Kiev Provinces) revealed deterioration of drug metabolism in liver. Experimental data indicated as well suppression of the microsomal drug-metabolizing system of liver caused by long-term exposure of the body to low-dose ionizing radiation. The results obtained should be taken into consideration in such patients for the slowed down drug metabolism in liver may provoke side effects.