Biofactors - Volume 34, issue 4

Article Type: Other

DOI: 10.3233/BIO-2009-1087

Citation: BioFactors, vol. 34, no. 4, pp. 261-261, 2008

Authors: Unno, Keiko | Ishikawa, Yuichi | Takabayashi, Fumiyo | Sasaki, Toru | Takamori, Nina | Iguchi, Kazuaki | Hoshino, Minoru

Article Type: Research Article

Abstract: Oxidative damage is believed to be an important cause of senescence. We have previously found that green tea catechins (GT-catechin), potent antioxidants, decrease oxidative damage to DNA and suppress brain dysfunction in aged senescence-accelerated mice (SAMP10) when ingested from the age of 1 month to the age of 12 months. To clarify the effect of GT-catechin on suppression of brain senescence, we investigated the effect of starting period to ingest GT-catechin. Six- or 9-month-old SAMP10 mice …were allowed free access to water containing 0.02% GT-catechin. SAMP10 mice exhibit senescence characteristics such as shortened life span, atrophied forebrain and lowered learning and memory abilities. Learning ability was significantly higher in mice that ingested GT-catechin from the age of 6 months to 12 months when compared with same-aged control mice drank water without GT-catechin. Starting GT-catechin intake from the age of 9 months tended to improve learning ability. The ages of 6 and 9 months are thought to be adult and middle ages, respectively in SAMP10 mice. This result suggested that GT-catechin was helpful in suppressing brain dysfunction with aging even when ingestion started at the adult age. Show more

Keywords: Green tea catechin, brain dysfunction, adulthood, oxidative damage, loss of synapse

DOI: 10.3233/BIO-2009-1080

Citation: BioFactors, vol. 34, no. 4, pp. 263-271, 2008

Authors: Batra, Vipen | Lakhmy, Seetha | Devasagayam, Thomas Paul Asir

Article Type: Research Article

Abstract: There is lot of interest in the folate metabolism because of the essential role of folate coenzymes in nucleic acid synthesis. Gamma (γ) radiation is well known for inducing damage in the DNA. To counteract these damage, a variety of DNA repair pathways have evolved that require regular supply of DNA bases whose biosynthesis in turn depends on sufficient pools of folate dependent enzymes like dihydrofolate reductase (DHFR). In the present study, we examined the ionizing …radiation mediated perturbation of DHFR activity in folate deficient and folate sufficient conditions. In folate deficient animals a potent inhibition of liver DHFR activity was observed. Our results showed that combination of folate starvation and ionizing radiation might adversely affect the DHFR activity, compared to their individual treatments. Measurement of apurinic/apyrimidinic sites (AP sites), a major type of DNA damage generated by radiation induced loss of purine and/or pyrimidine base, indicated a dose dependent DNA damage in folate deficient animals. In conclusion our data suggest an interactive role of folate deficiency and radiation injury in inhibiting DHFR activity. Show more

Keywords: γ-radiation, folate, dihydrofolate reductase, mice, starvation, AP sites

DOI: 10.3233/BIO-2009-1081

Citation: BioFactors, vol. 34, no. 4, pp. 273-283, 2008

Authors: Wada, Naoki | Wakami, Hirotaka | Konishi, Tetsuya | Matsugo, Seiichi

Article Type: Research Article

Abstract: α-Lipoic acid (LA) and its reduced form dihydrolipoic acid (DHLA) are well known as strong antioxidants. LA has the characteristic distorted five membered 1,2-dithiolane ring, which is quite vulnerable to UV irradiation. The UV induced decomposition of LA and the effect of the following addition of biothiols to the photoirradiated solution of LA were investigated by UV-vis spectrometry and ^{1} H NMR spectral analysis. The mechanism of UV irradiated LA decomposition was proposed based on …the results obtained from NMR and GPC measurements. Show more

Keywords: α-lipoic acid, biothiol, disulfide interchange reaction

DOI: 10.3233/BIO-2009-1082

Citation: BioFactors, vol. 34, no. 4, pp. 285-292, 2008

Authors: Nakabayashi, Hideo | Hashimoto, Takashi | Ashida, Hitoshi | Nishiumi, Shin | Kanazawa, Kazuki

Article Type: Research Article

Abstract: To understand the mechanisms of the anti-obesity effects of dietary caffeine, the effects of caffeine and its metabolites on adipocyte differentiation and insulin-stimulated glucose uptake in murine 3T3-L1 adipocytes were investigated. Caffeine did not inhibit the differentiation of 3T3-L1 pre-adipocytes to mature adipocytes, but it did suppress the intracellular lipid accumulation after complete differentiation in a dose-dependent manner (0.125–1.0 mM). This effect was also observed in 1,3,7-trimethyluric acid- 3,7-dimethyluric acid- and …5-acetylamino-6-formylamino-3-methyluracil-treated cells. Caffeine also inhibited insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes in a dose-dependent manner. Treatment with theophylline, paraxanthine, 1-methylxanthine (MX), 3-MX, or 7-MX also inhibited glucose uptake in differentiated adipocytes. These results suggest that the anti-obesity activity of dietary caffeine is due to the additive and/or synergistic inhibitory effects of caffeine and its metabolites on intracellular lipid accumulation and that caffeine does not affect adipocyte differentiation. Show more

Keywords: Caffeine, caffeine metabolites, 3T3-L1 adipocytes, glucose uptake, adipocyte differentiation

DOI: 10.3233/BIO-2009-1083

Citation: BioFactors, vol. 34, no. 4, pp. 293-302, 2008

Authors: Wen, Zhaoyang | Shi, Zhengming | Feng, Ping | Xue, Xiaowei | Dong, Kun | Wang, Xuejiang

Article Type: Research Article

Abstract: Aim: To elucidate the anticancer mechanism of Huqi San by assessing the expression of G-6-Pase, SDH, ATPase and AFP in N-nitrosodiethylamine-mediated hepatocarcinogenesis in rats. Methods: A Solt-Farber two-step test model of hepatocarcino genesis was established by diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) in rats to investigate the modifying effects of expression of 6-glucosephosphatase (G-6-Pase), succinodehydrogenase (SDH), adenosine triphosphatase (ATPase) in N-nitrosodiethylamine-mediated hepatocarcinogenesis. Hu Qisan compounded by eight medicinal herbs was prepared …in glycoprival granules with wich 0.38 g crude herbs/mL solution was prepared for administration. γ-Glutamy-transpeptidase (γ-GT), G-6-Pase, SDH and ATPase were immunohistochemically determined. The activity of alpha-fetoglobulin (AFP) in the livers was measured with Immunofluorescence. Results: Huqi San treated rats showed significant decrease in areas of γ-GT positive foci (P< 0.001). On the other hand, the expression of G-6-Pase, SDH and ATPase has obviously altered in Huqi San treated group. The activity of AFP also significantly decreased after the treatment with Huqi San (8 g/kg body weight or 4 g/kg body weight) or total alkali of mistletoe (0.12 g/kg body weight). Conclusions: Huqi San can obviously increase these activities of G-6-Pase, SDH and ATPase, and at the same time significantly decrease the expression of γ-GT and AFP. Therefore, it can obstruct or inhibit the rat's liver preneolastic lesion induced by DEN. Show more

Keywords: Chinese herbs, hepatocarcinogenesis, liver preneolastic lesion, metabolic enzyme, diethylnitrosoamine (DEN) hepatocarcinogenesis

DOI: 10.3233/BIO-2009-1084

Citation: BioFactors, vol. 34, no. 4, pp. 303-312, 2008

Authors: Morceau, Franck | Buck, Isabelle | Dicato, Mario | Diederich, Marc

Article Type: Research Article

Abstract: Constitutive tyrosine kinase activity of the breakpoint cluster region (Bcr)-Abl fusion protein is characteristic of chronic myelogenous leukemia (CML). As resistance against Imatinib a Bcr-abl inhibitor used in CML, was described, Heat shock protein (Hsp90) became an alternative target as inhibition of Bcr-Abl-Hsp90 complex leads to proliferation arrest. Here, we used natural product Radicicol (Rad), a macrocyclic antifungal, as an Hsp90 inhibitor to investigate the effect of Bcr-Abl inactivation on erythroid gene …expression and subsequently on the transcription factors involved in their regulation. We showed that all erythroid genes studied were over-expressed after Rad treatment while Bcr-Abl expression was inhibited. Specific transcription factor NF-E2 was induced in Rad-treated cells as well as GATA-1 cofactors Friend of GATA (FOG)1 and SP1, whereas PU.1 was downregulated. Moreover, p38 mitogen activated protein kinase (MAPK) inhibition prevented Rad-mediated differentiation of K562 in correlation with decreased γ-globin expression and suppression of Rad-mediated inhibition of PU.1. In conclusion, our results show that Radicicol leads to Bcr-Abl inactivation via Hsp90 inhibition inducing reactivation of the erythroid program in K562 cells. Show more

Keywords: Erythroid genes, radicicol, Bcr-Abl, Hsp90, PU.1, p38MAPK

DOI: 10.3233/BIO-2009-1085

Citation: BioFactors, vol. 34, no. 4, pp. 313-329, 2008

Authors: Ko, Kam Ming | Chen, Na | Leung, Hoi Yan | Leong, Eriol P.K. | Poon, Michel K.T. | Chiu, Po Yee

Article Type: Research Article

Abstract: Mitochondrial decay is a major cause of aging, leading to the subsequent death of aerobic organisms including humans. In the present study, we examined the effects of supplementation with schisandrin B (Sch B, a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis), administered at 0.012% (w/w) of diet, starting from the age of 36 weeks, on age-dependent changes in mouse mitochondrial antioxidant status and functional ability in various tissues (brain, heart, liver, and kidney) up …to the age of 120 weeks. We also monitored survival of male and female C57BL/6J mice. Aging caused progressive impairment in mitochondrial antioxidant status in various tissues, as evidenced by decreases in reduced glutathione and α-tocopherol levels, and Mn-superoxide dismutase activity. Impairments in mitochondrial antioxidant status were invariably associated with increases in mitochondria-driven reactive oxygen species (ROS) production in tissue homogenates, as well as decreased mitochondrial ATP-generation capacities (ATP-GCs), in all tested tissues. Diet supplementation with Sch B ameliorated impairment in mitochondrial antioxidant status during aging. The effects were more pronounced in younger than in older mice, when compared to age-matched non-supplemented controls. Sch B supplementation also suppressed mitochondria-driven ROS production and enhanced mitochondrial ATP-GC in various tissues during aging. The beneficial effects of Sch B supplementation on mitochondrial antioxidant status and functional ability were paralleled by survival improvement in aging male mice, when compared with controls. Sch B supplementation also improved the survival in female mice. In conclusion, long-term Sch B supplementation mitigated age-dependent impairments in mitochondrial antioxidant capacity and functional ability, thereby retarding the aging process in mice, particularly during early aging. Show more

Keywords: Schisandrin B, aging, mitochondria, glutathione, α-tocopherol, Mn-superoxide dismutase, reactive oxygen species, ATP generation, brain, heart, kidney, liver

DOI: 10.3233/BIO-2009-1086

Citation: BioFactors, vol. 34, no. 4, pp. 331-342, 2008