Galectin-1-Induced Autophagy Facilitates Cisplatin Resistance of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers in Taiwan. Although chemotherapy is the primary treatment for HCC patients, drug resistance often leads to clinical failure. Galectin-1 is a beta-galactoside binding lectin which is up-regulated in HCC patients and promotes tumor growth by mediating cancer cell adhesion, migration and proliferation, but its role in chemoresistance of HCC is poorly understood. In this study we found that galectin-1 is able to lead to chemoresistance against cisplatin treatment, and subsequent inhibition has reversed the effect of cell death in HCC cells. Moreover, galectin-1 was found to induce autophagic flux in HCC cells. Inhibition of autophagy by inhibitors or knockdown of Atg5 cancels galectin-1-induced cisplatin resistance in HCC cells. Increase of mitophagy triggered by galectin-1 was found to reduce the mitochondrial potential loss and apoptosis induced by cisplatin treatment. Finally, using an in situ hepatoma mouse model, we clearly demonstrated that inhibition of galectin-1 by thiodigalactoside could significantly augment the anti-HCC effect of cisplatin. Taken together, our findings offer a new insight into the chemoresistance galectin-1 causes against cisplatin treatment, and points to a potential approach to improve the efficacy of cisplatin in the treatment of HCC patients.     

Tetrazolium Reduction by Guard Cells in Abaxial Epidermis of Vicia faba: Blue Light Stimulation of a Plasmalemma Redox System

The stomata in the abaxial epidermis of Vicia faba were examined for the location of redox systems using tetrazolium salts. Three distinct redox systems could be demonstrated: chloroplast, mitochondrial, and plasmalemma. The chloroplast activity required light and NADP. Mitochondrial activity required added NADH and was suppressed by preincubation with KCN. The plasmalemma redox system in guard cells also required NADH, but was insensitive to KCN and was stimulated by blue light. The involvement of an NADH dehydrogenase in the blue light stimulated redox system in guard cells was suggested by the sensitivity to plantanetin, an inhibitor of NADH dehydrogenase. The redox system of mitochondria was the most active followed by that of plasmalemma. The activity of chloroplasts was the least among the three redox systems. The plasmalemma mediated tetrazolium reduction was stimulated by exogenous flavins and suppressed by Kl or phenylacetate, inhibitors of flavin excitation. We therefore conclude that an NADH-dependent, flavin mediated electron transport system, sensitive to blue light, operates in the plasmalemma of guard cells.     

Queen succession in the primitively eusocial tropical waspRopalidia marginata (Lep.) (Hymenoptera: Vespidae)

Females of the primitively eusocial wasp Ropalidia marginata can be classified into three behavioral groups: Sitters, Fighters, and Foragers. It has been speculated that both Sitters and Fighters may be hopeful queens and that the Foragers may have little or no opportunities for direct reproduction. Here we show that in 9 of 12 queen-removal experiments where such a behavioral differentiation could be discerned, the individual that became a queen (the potential queen) was a Sitter in 6 cases, a Fighter in 2 cases, and a Forager in only 1 case. Although potential queens spent significantly more time absent from the nest and showed significantly higher rates of dominance behavior compared to the mean values for nonqueens in their colonies, they were intermediate with respect to all behaviors and age when compared to the range of values for nonqueens in their colonies. Potential queens were not necessarily the highest-ranking individuals among the nonqueens. The pattern of queen succession in this species appears to be quite different from the temperate pattern, where an old and active forager of high dominance rank is the potential queen. Although somewhat similar to the tropical pattern of a relatively younger female that has performed relatively little foraging being the potential queen, it is perhaps more accurate to describe the potential queens of R. marginata as unspecialized intermediates.     

Structure and function of disk aggregates of the coat protein of tobacco mosaic virus

Experiments have been carried out on the coat protein of tobacco mosaic virus (TMVP) to test for the occurrence of the previously postulated RNA-induced direct switching, during in vitro assembly of tobacco mosaic virus (TMV), of the subunit packing from the cylindrical bilayer disk to the virus helical arrangement. No evidence was found for such RNA-induced switching and no evidence for the direct participation of the bilayer disk in either the nucleation or elongation phases of the in vitro virus assembly. Instead, virus assembly proceeds by an initiation step involving the binding of the RNA to the previously characterized two-plus turn helical aggregate that is formed from small oligomers of subunits. However, a bilayer disk, which has been characterized in high ionic strength crystals, has been observed in low ionic strength virus assembly solutions only as a transient species upon depolymerization of dimers of bilayer disks formed in solution at high ionic strength, and not as an equilibrium species of TMVP.     

Unique rearrangement of ergocalciferol side chain in vitro: production of a biologically highly active homologue of 1,25-dihydroxyvitamin D3

In vitro incubation of 24-epi-25-hydroxyvitamin D2 with chicken kidney homogenate produced several compounds, one of which had an affinity equal to that of 1,25-dihydroxyvitamin D2 for the chick intestinal receptor. The affinity of 24-epi-1,25-dihydroxyvitamin D2 for the same receptor was found to be half that of 1,25-dihydroxyvitamin D2. The unknown compound was produced only when homogenate was prepared from pooled kidneys taken from both vitamin D deficient and replete chickens. The compound has been tentatively identified as 1,25-dihydroxy-22-dehydro-26-homovitamin D3 by ultraviolet absorption spectrophotometry and mass spectrometry. Chemical synthesis of 1,25-dihydroxy-22-dehydro-26-homovitamin D3 provided additional evidence for the structure. Administration of this 26-homologue of 1,25-dihydroxyvitamin D3 at the dose level of 650 pmol/rat stimulated bone calcium mobilization in the hypocalcemic rat equal to that of 1,25-dihydroxyvitamin D3. Thus, this paper demonstrates unique methyl migration on the side chain of 24-epi-1,25-dihydroxyvitamin D3 to form a more biologically potent analogue.     

Prediction and comparison of the secondary structure of legume lectins

Secondary structure prediction for the 4 legume lectins: Concanavalin A, soybean agglutinin, favabean lectin and lentil lectin, was done by the method of Chou and Fasman. This prediction shows that these four lectins fall into a structurally distinct class of proteins, containing high amounts of β-sheet and β-turns. There is a notable similarity in the gross structure of these proteins; all four of them contain about 40–50% of β-sheet, 35–45 % β-turn and 0–10% of α-helix. When the secondary structure of corresponding residues in each pair of these lectins was compared, there was a striking similarity in the Concanavalin A-soybean agglutinin and favabean lectin-lentil lectin pairs, and considerably less similarity in the other pairs, suggesting that these legume lectins have probably evolved in a divergent manner from a common ancestor. A comparison of the predicted potential β-turn sites also supports the hypothesis of divergent evolution in this class of lectins.     

Photosynthetic Units and Carbon Assimilation in Leaves of Grain Sorghum under Different Light Intensities

The Cyt f and P700 contents in leaves of three Sorghum, varietieswere measured, in relation to their carbon assimilation, underdifferent light intensities during growth. At the maximum irradiationused (1,800 µE m^–2 s^–1) the ratio of P700to Cyt f was close to unity, whereas under low irradiation (450µE m^–2 s^–1) the ratio of P700 to Cyt f rangedfrom two to three. A strikingly positive correlation existedbetween the P700 contents of the leaves and their rates of carbondioxide fixation, dry matter production and Cyt f contents,only when the plants were grown under high light intensities.The P700 content of the leaves in plants grown under low irradiationwas unrelated to the contents of Cyt f. Thus, at a high lightintensity there is a close relationship between the Cyt f andP700 levels, but at low intensities the amounts of electroncarriers and the reaction centre are independent. (Received March 7, 1983; Accepted August 24, 1983)     

Beneficial interaction between photosynthesis and respiration in mesophyll protoplasts of pea during short light-dark cycles

The respiratory uptake or photosynthetic evolution of oxygen by mesophyll protoplasts of pea ( Pisum sativum L. cv. Arkel) were monitored during successive short. (3–5 min) cycles of darkness and illumination. The rate of respiration was nearly doubled after 3–4 short periods of illumination while there was a 15–20% enhancement in photosynthesis with cycles of illumination and darkness preceding illumination. Such interaction between photosynthesis and respiration was statistically significant when bicarbonate was present in the reaction medium. The inhibitors of photosynthesis [3(3,4–dichlorophenyl)-l,l-dimethylurea (DCMU), glyceraldehyde] decreased respiration after periods of illumination, whereas inhibitors of respiratory electron transport (Rotenone, antimycin A, NaN₃) suppressed photosynthesis, as well. We suggest that a rapid beneficial interaction exists between photosynthesis and respiration in protoplasts, even during short cycles of light and darkness.     

l-[3H]Nitroarginine and l-[3H]Arginine Uptake into Rat Cerebellar Synaptosomes: Kinetics and Pharmacology

Abstract: Characteristics of the transport of the nitric oxide synthase substrate l -arginine and its inhibitor, N ^G-nitro- l -arginine ( l -NOARG), into rat cerebellar synaptosomes were studied. Uptake of both l -arginine and l -NOARG was linear with increasing amount of protein (up to 40 µg) and time of incubation (up to 5 min) at 37°C. Uptake of both compounds reached a steady state by 20 min. Maximal uptake of l -NOARG (650 pmol/mg of protein) was three to four times higher than that of l -arginine (170 pmol/mg of protein). l -NOARG uptake showed biphasic kinetics ( K _{m 1} = 0.72 m M , V _{max 1} = 0.98 nmol/min/mg of protein; K _{m 2} = 2.57 m M , V _{max 2} = 16.25 nmol/min/mg of protein). l -Arginine uptake was monophasic with a K _m of 106 µ M and a V _max of 0.33 nmol/min/mg of protein. l -NOARG uptake was selectively inhibited by l -NOARG, N ^G-nitro- l -arginine methyl ester, and branched-chain and aromatic amino acids. l -Alanine and l -serine also inhibited l -NOARG uptake but with less potency. Uptake of l -arginine was selectively inhibited by N ^G-monomethyl- l -arginine acetate and basic amino acids. These studies suggest that in rat cerebellar synaptosomes, l -NOARG is transported by the neutral amino acid carrier systems T and L with high affinity, whereas l -arginine is transported by the basic amino acid carrier system y⁺ with high affinity. These data indicate that the concentration of competing amino acids is an important factor in determining the rates of uptake of l -NOARG and l -arginine into synaptosomes and, in this way, may control the activity of nitric oxide synthase.