Biofactors - Volume 11, issue 4

Authors: Terasawa, Yoshimitsu | Manabe, Hiroki | Yoshida, Norimasa | Uemura, Manabu | Sugimoto, Naohito | Naito, Yuji | Yoshikawa, Toshikazu | Kondo, Motoharu

Article Type: Research Article

Abstract: α‐Tocopherol supplementation is reported to protect against cardiovascular disease and to influence cells involved in atherogenesis, such as monocytes. Interactions between monocytes and vascular endothelial cells occur early in atherogenesis, and adhesion is mediated by integrins. We evaluated the effects of α‐tocopherol on expression of Mac‐1 (CD11b/CD18) by monocytes after stimulation with oxidized low‐density lipoprotein (LDL), which is implicated as a potent chemotactic agent in atherogenesis. Incubation of whole blood with oxidized LDL (100 μg/ml) increased Mac‐1 expression on monocytes, and preincubation with α‐tocopherol reduced this upregulation in a concentration dependent manner. In another experiment, whole blood was obtained …from healthy adult volunteers after 10 days of α‐tocopherol administration (600 mg/day) and was incubated with oxidized LDL (100 μg/ml). There was a decrease in the upregulation of Mac‐1 compared with that measured before administration. Adherence of oxidized LDL‐stimulated monocytes to human umbilical vein endothelial cells was reduced by pretreatment with α‐tocopherol, and was also inhibited by an anti‐CD18 monoclonal antibody. Experiments with protein kinase C inhibitors suggested that reduction of Mac‐1 upregulation by α‐tocopherol was secondary to a decrease of protein kinase C activity. In conclusion, α‐tocopherol suppressed the upregulation of Mac‐1 expression on monocytes by oxidized LDL. Show more

Keywords: α‐Tocopherol, Mac‐1, oxidized LDL, monocytes, protein kinase C

Citation: Biofactors, vol. 11, no. 4, pp. 221-233, 2000

Authors: Shibata, Hideyuki | Kimura‐Takagi, Itsuko | Nagaoka, Masato | Hashimoto, Shusuke | Aiyama, Ritsuo | Iha, Masahiko | Ueyama, Sadao | Yokokura, Teruo

Article Type: Research Article

Abstract: To elucidate the anti‐ulcer potential of Cladosiphon fucoidan, anti‐peptic activity, bFGF stabilizing activity and inflammatory properties of this and related substances were investigated. Anti‐peptic activity was observed with this and other sulfated polysaccharides such as dextran sulfate, carrageenan, and Fucus fucoidan. However, non‐sulfated polysaccharides such as mannan and dextran did not exert the anti‐peptic activity. The loss of bFGF bioactivity was prevented by all sulfated polysaccharides tested except chondroitin sulfate, at pH 7.4 and at pH 4.0. At pH 2.0, only heparin protected the bFGF activity. The generation of superoxide by macrophages and PMNs was stimulated by dextran sulfate, carrageenan, …and Fucus fucoidan, whereas Cladosiphon fucoidan, heparin and chondroitin did not. Dextran sulfate, carrageenan, and Fucus fucoidan also stimulated the secretion of TNFα from macrophages, while Cladosiphon fucoidan did not. Thus, Cladosiphon fucoidan is a sulfated polysaccharide without inflammatory action. These results suggest that Cladosiphon fucoidan is a safe substance with potential for gastric protection. Show more

Keywords: Cladosiphon okamuranus tokida, fucoidan, anti‐peptic activity, bFGF, superoxide, TNFα

Citation: Biofactors, vol. 11, no. 4, pp. 235-245, 2000

Authors: Mittal, Rashmi A. | Tan, Chee‐Hong | Khoo, Hoon‐Eng

Article Type: Research Article

Abstract: Adenosine is known to modulate cell growth in a variety of mammalian cells either via the activation of receptors or through metabolism. We investigated the effect of adenosine on Baby Hamster Kidney (BHK) cell growth and attempted to determine its mechanism of modulation. In wild‐type BHK cells, adenosine evoked a biphasic response in which a low concentration of adenosine (1–5 μM) produced an inhibition of colony formation but at higher concentrations (up to 50 μM) this inhibition was progressively reversed. However, no biphasic response was observed in an “adenosine kinase” deficient BHK mutant, “5a”, which suggests that adenosine kinase plays …an important role in the modulation of growth response to adenosine. Adenosine receptors did not appear to have a role in regulating cell growth of BHK cells. Specific A1 and A2 receptor antagonists were unable to reverse the effect of adenosine on cell growth. Even though a specific A3 adenosine receptor antagonist MRS‐1220 partly reversed the inhibition in colony formation at 1 μM adenosine, it also affected the transport of adenosine. Thus adenosine transport and metabolism appears to play the major role in this modulation of cell growth as 5′ ‐amino‐5′ ‐deoxyadenosine, an adenosine kinase inhibitor, reversed the inhibition of cell growth observed at 1 μM adenosine. These results, taken together, would suggest that adenosine modulates cell growth in BHK mainly through its transport and metabolism to adenine nucleotides. Show more

Keywords: Baby hamster kidney cells, adenosine, cell growth, receptors, adenosine kinase

Citation: Biofactors, vol. 11, no. 4, pp. 247-256, 2000

Authors: Fujita, Noriko | Manabe, Hiroki | Yoshida, Norimasa | Matsumoto, Naohito | Ochiai, Jun | Masui, Yasuharu | Uemura, Manabu | Naito, Yuji | Yoshikawa, Toshikazu

Article Type: Research Article

Abstract: Cardiovascular tissue injury in ischemia/reperfusion has been shown to be prevented by angiotensin‐converting enzyme (ACE) inhibitors. However, the mechanism on endothelial cells has not been assessed in detail. Cultured human aortic endothelial cells (HAEC) were exposed to hypoxia with or without reoxygenation. Hypoxia enhanced apoptosis along with the activation of caspase‐3. Reoxygenation increased lactate dehydrogenase release time‐dependently, along with an increase of intracellular oxygen radicals. ACE inhibitor quinaprilat and bradykinin significantly lessened apoptosis and lactate dehydrogenase release with these effects being diminished by a kinin B2 receptor antagonist and a nitric oxide synthase inhibitor. In conclusion, hypoxia activated the suicide …pathway leading to apoptosis of HAEC by enhancing caspase‐3 activity, while subsequent reoxygenation induced necrosis by enhancing oxygen radical production. Quinaprilat could ameliorate both apoptosis and necrosis through the upregulation of constitutive endothelial nitric oxide synthase via an increase of bradykinin, with the resulting increase of nitric oxide. Show more

Keywords: Endothelial cell, hypoxia, apoptosis, ACE inhibitor, nitric oxide

Citation: Biofactors, vol. 11, no. 4, pp. 257-266, 2000

Article Type: Other

Citation: Biofactors, vol. 11, no. 4, pp. 267-268, 2000