Involvement of tumor necrosis factor receptor-associated protein 1 (TRAP1) in apoptosis induced by beta-hydroxyisovalerylshikonin

beta-Hydroxyisovalerylshikonin (beta-HIVS), a compound isolated from the traditional oriental medicinal herb Lithospermum radix, is an ATP non-competitive inhibitor of protein-tyrosine kinases, such as v-Src and EGFR, and it induces apoptosis in various lines of human tumor cells. However, the way in which beta-HIVS induces apoptosis remains to be clarified. In this study, we performed cDNA array analysis and found that beta-HIVS suppressed the expression of the gene for tumor necrosis factor receptor-associated protein 1 (TRAP1), which is a member of the heat-shock family of proteins. When human leukemia HL60 cells and human lung cancer DMS114 cells were treated with beta-HIVS, the amount of TRAP1 in mitochondria decreased in a time-dependent manner during apoptosis. A similar reduction in the level of TRAP1 was also observed upon exposure of cells to VP16. Treatment of DMS114 cells with TRAP1-specific siRNA sensitized the cells to beta-HIVS-induced apoptosis. Moreover, the reduction in the level of expression of TRAP1 by TRAP1-specific siRNA enhanced the release of cytochrome c from mitochondria when DMS114 cells were treated with either beta-HIVS or VP16. The suppression of the level of TRAP1 by either beta-HIVS or VP16 was blocked by N-acetyl-cysteine, indicating the involvement of reactive oxygen species (ROS) in the regulation of the expression of TRAP1. These results suggest that suppression of the expression of TRAP1 in mitochondria might play an important role in the induction of apoptosis caused via formation of ROS.     

Δ16-Dehydroadynerigenin glycosides of Nerium odorum

β-d-Diginoside and β-d-digitaloside of Δ¹⁶-dehydroadynerigenin were isolated from the oven dried leaves of Nerium odorum.     

Relationship between plasma asymmetric dimethylarginine and nitric oxide levels affects aerobic exercise training-induced reduction of arterial stiffness in middle-aged and older adults

[Purpose]Aerobic exercise training (AT) reverses aging-induced deterioration of arterial stiffness via increased arterial nitric oxide (NO) production. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, was decreased by AT. However, whether AT-induced changes in ADMA levels are related to changes in nitrite/nitrate (NOx) levels remains unclear. Accordingly, we aimed to clarify whether the relationship between plasma ADMA and NOx levels affected the AT-induced reduction of arterial stiffness in middle-aged and older adults.[Methods]Thirty-one healthy middle-aged and older male and female subjects (66.4 ± 1.3 years) were randomly divided into two groups: exercise intervention and sedentary controls. Subjects in the training group completed an 8-week AT (60%–70% peak oxygen uptake [V˙O2peak] for 45 min, 3 days/week).[Results]AT significantly increased V˙O2peak (p < 0.05) and decreased carotid β-stiffness (p < 0.01). Moreover, plasma ADMA levels were significantly decreased while plasma NOx levels and NOx/ADMA ratio were significantly increased by AT (p < 0.01). Additionally, no sex differences in AT-induced changes of circulating ADMA and NOx levels, NOx/ADMA ratio, and carotid β-stiffness were observed. Furthermore, the AT-induced increase in circulating ADMA levels was negatively correlated with an increase in circulating NOx levels (r = -0.414, p < 0.05), and the AT-induced increase in NOx/ADMA ratio was negatively correlated with a decrease in carotid β-stiffness (r = -0.514, p < 0.01).[Conclusion]These results suggest that the increase in circulating NOx with reduction of ADMA elicited by AT is associated with a decrease in arterial stiffness regardless of sex in middle-aged and older adults.     

Responses of ring widths and maximum densities of Larix gmelinii to climate on contrasting north- and south-facing slopes in central Siberia

An analysis was performed of the climatic responses of the radial growth of Larix gmelinii (Rupr.) Rupr. at two sites—both of which included contrasting north- and south-facing slopes—in Tura, central Siberia, with the development of ring width and maximum-density chronologies for each slope. Both residual and standard chronologies of ring widths were positively correlated with temperature from late May until mid June on all four slopes. By contrast, standard chronologies of ring widths were negatively correlated with precipitation during the winter (from October to April) and in May on the north-facing slope at site 1 and on the south-facing slope at site 2 respectively. The negative correlations with precipitation during the winter and in May on some of the slopes suggested that delayed snowmelt in early spring might inhibit the radial growth of L. gmelinii, and the effects of snow are likely to vary with topography. Both residual and standard chronologies of maximum densities were positively correlated with temperature in early July on all four slopes. Maximum densities were also positively correlated with precipitation during summer of the previous year on all the slopes. These suggest that no major differences exist in terms of responses of maximum density to climatic factors between the north- and south-facing slopes.     

Gene action for surrogate traits of water-use efficiency and harvest index in peanut (Arachis hypogaea)

Low peanut productivity in the semi‐arid tropics is attributed mainly to drought caused by low and erratic rainfall. Genetic improvement in water‐use efficiency (WUE) could potentially lead to improved yield under limited moisture availability. In peanut, WUE is correlated with SPAD chlorophyll meter reading (SCMR), specific leaf area (SLA), and carbon isotope discrimination (Δ¹³C). These traits can be used as surrogates for selecting for WUE. Partitioning of assimilates as measured by the harvest index (HI) has the greatest effect on pod yield. To improve these traits for tailoring peanut genotypes well matched for water‐limited conditions, a good knowledge of genetic systems controlling the expression of these traits is essential. This study was undertaken to work out the gene action for the surrogates of WUE and HI in a 6 × 6 full diallel mating design. Two of the studied surrogates (SCMR and Δ¹³C) for WUE were found to be under the influence of both additive and nonadditive gene effects with preponderance of the former. SLA and HI were controlled by genes that are mainly additive in nature. Selection for these traits can be effective in the early generations. Maternal effects observed for SLA and Δ¹³C are suggestive of the crucial role of selection of female parent in improvement of these traits. The parental lines, TMV 2 NLM (for SCMR, SLA and Δ¹³C) and ICGV 86031 (for SCMR and SLA), were found to be good general combiners each for more than one character. TAG 24 and Chico (for HI) and CSMG 84‐1 (for SLA) were the other good general combiners.     

Evolution of insulin-like growth factor I (IGF-I): structure and expression of an IGF-I precursor from Xenopus laevis

By means of a cloning strategy employing the polymerase chain reaction, we have isolated and characterized cDNAs for Xenopus laevis insulin-like growth factor I (IGF-I). These cDNAs encode a primary IGF-I translation product of 153 residues that demonstrates considerable amino acid sequence similarity with IGF-IA peptides from other species. Fifty-seven of 70 residues of the mature protein are identical among human, rat, chicken, and Xenopus IGF-I, while less amino acid conservation is found at the COOH-terminus (25/35 identities) or at the NH2-terminus (24/48 identities) of the precursor protein. Despite the lower degree of structural similarity at the NH2-terminus, in vitro studies of IGF-I biosynthesis and proteolytic processing support a conserved function for the atypically long 48 residue NH2-terminal signal sequence in directing the nascent IGF-I peptide through the secretory pathway. The 5'-untranslated region of Xenopus IGF-I mRNA matches the human, rat, and chicken sequences in greater than 90% of 279 nucleotides. IGF-I mRNAs from all four species encode a conserved upstream open reading frame of 14 amino acids starting 240-250 nucleotides 5' to the translation start site, suggesting a possible role for this region in modulating IGF-I gene expression. The X. laevis IGF-I gene is transcribed and processed into three mRNAs of 1.6, 2.1, and 3.0 kilobases in liver, and IGF-I mRNAs can be detected in liver, lung, heart, kidney, and peritoneal fat of adult animals. These studies demonstrate that both the IGF-I protein precursor and potential regulatory regions of IGF-I mRNA have been conserved during vertebrate evolution, and indicate that like several other polypeptide growth factors, IGF-I may be of fundamental importance in regulating specific aspects of growth and development in all vertebrates.     

Antioxidant effect of caeruloplasmin on microsomal lipid peroxidation

Microsomal NADPH-dependent lipid peroxidation catalyzed by ADP-Fe³⁺ was inhibited by the addition of caeruloplasmin. The antioxidant effect of caeruloplasmin was independent of the superoxide anion (O^?₂ scavenging activity. Since caeruloplasmin enhanced the function of ADP-Fe³⁺ acting as electron acceptor for microsomal electron transport system, the antioxidant effect of caeruloplasmin is considered to depend on the ferroxidase activity.