Shuichi Nozaki

Publications (6)12.02 Total impact

• Article: Molecular Defect and Atherogenicity in Cholesteryl Ester Transfer Protein Deficiency

  KEN‐ICHI HIRANO, SHIZUYA YAMASHITA, NAOHIKO SAKAI, TAKESHI ARAI, YU YOSHIDA, SHUICHI NOZAKI, KAORU KAMEDA‐TAKEMURA, YUJI MATSUZAWA
  Annals of the New York Academy of Sciences 12/2006; 748(1):599 - 602. · 3.15 Impact Factor
• Article: Analyses of genetic abnormalities in type I CD36 deficiency in Japan: identification and cell biological characterization of two novel mutations that cause CD36 deficiency in man

  Hirokazu Kashiwagi, Yoshiaki Tomiyama, Shuichi Nozaki, Teruo Kiyoi, Seiji Tadokoro, Kengo Matsumoto, Shigenori Honda, Satoru Kosugi, Yoshiyuki Kurata, Yuji Matsuzawa
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  ABSTRACT: To elucidate genetic abnormalities in type I CD36 deficiency, we analyzed 28 Japanese subjects whose platelets and monocytes/macrophages lacked CD36 on their surface. We identified two novel mutations in the CD36 gene. One was a complex deletion/insertion mutation, in which 3 bp, GAG, were deleted at nucleotide (nt) 839-841, and 5 bp, AAAAC, were inserted at the same position (839-841del&#77insAAAAC). Mutation 839-841del&#77insAAAAC led to a frameshift and appearance of a premature stop codon; it was also accompanied with a marked reduction in the amount of CD36 mRNA. The other was a 12-bp deletion at nt 1438-1449 (1438-1449del) accompanied with or without skipping of exon 9 (nt 959-1028). Mutation 1438-1449del led to an inframe 4-amino-acid deletion, whereas exon 9 skipping led to a frameshift and the appearance of a premature stop codon. Expression assay revealed that both 1438-1449del and exon 9 skipping directly caused impairment of the surface expression of CD36. A survey of the five known mutations including 839-841del&#77insAAAAC and 1438-1449del in type I CD36-deficient subjects demonstrated that the five mutations covered more than 90% of genetic defects among them and that the substitution of T for C at nt 478 (478C&#77T) was the most common mutation with more than 50% frequency. However, none of the four subjects that possessed isoantibodies against CD36 had 478C&#77T, suggesting that 478C&#77T prevents the production of isoantibodies against CD36.
  Human Genetics 05/2001; 108(6):459-466. · 5.07 Impact Factor
• Article: Reduced Adhesion of Monocyte-Derived Macrophages from CD36-Deficient Patients to Type I Collagen

  Mohamed Janabi, Shizuya Yamashita, Ken-ichi Hirano, Kengo Matsumoto, Naohiko Sakai, Hisatayo Hiraoka, Hirokazu Kashiwagi, Yoshiaki Tomiyama, Shuichi Nozaki, Yuji Matsuzawa
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  ABSTRACT: CD36 is an 88-kDa glycoprotein expressed on platelets and monocyte/macrophages (Mφ). CD36 is a multifunctional receptor for collagen, thrombospondin, oxidized low density lipoproteins (LDL), and long-chain fatty acids. The present study was performed to investigate whether CD36 can function as an adhesion molecule which is involved in mediating human macrophages (Mφ) adhesion to type I collagen in vitro. The Mφ of human CD36-deficient as well as normal control subjects were isolated and cultured on the multi-well plates coated with type I collagen, a natural ligand for CD36. Up to 2 h of incubation, the Mφ from CD36-deficient patients showed almost a ∼55% decrease in adhesion to type I collagen in comparison to those from controls (P < 0.01). However, there was no significant difference in the adhesion thereafter. Furthermore, the addition of antibody against CD36 into the media of control Mφ significantly inhibited the adhesion by ∼50% (P < 0.05). The addition of oxidized LDL (OxLDL) did not alter adhesion of Mφ from both CD36-deficient and controls. These data suggest that CD36 is involved in the adhesion of Mφ to type I collagen, especially in the early stage of adhesion.
  Biochemical and Biophysical Research Communications.
• Article: The role of hepatic triglyceride lipase in the metabolism of intermediate-density lipoprotein—Postheparin lipolytic activities determined by a sensitive, nonradioisotopic method in hyperlipidemic patients and normals

  Shuichi Nozaki, Masaharu Kubo, Hiroshi Sudo, Yuji Matsuzawa, Seiichiro Tarui
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  ABSTRACT: With a view to elucidating the physiologic role of hepatic triglyceride lipase (H-TGL), we studied the relationship between the activity of H-TGL and the concentrations of the lipids of ultracentrifugally separated lipoprotein fractions in sera from 81 cases of primary hyperlipidemia, 5 of hypothyroidism, and 31 normal subjects. The activity of H-TGL in postheparin plasma was determined by the sensitive, nonradioisotopic method that was recently developed by us. In the entire group of subjects including the normals, the activity of H-TGL had a significant inverse correlation with the concentration of the cholesterol (r = −0.443, P < 0.001) and phospholipid (r = −0.433, P < 0.001) of intermediate density lipoprotein (IDL). When the patients were divided into subgroups according to the phenotype of hyperlipidemia, it was found that the correlation was more significant in type IIb (r = 0.695, P < 0.001) or type IV + V (r = −0.664, P < 0.0001). In the five cases of hypothyroidism, the mean IDL cholesterol level was high (28.3 ± 12.3 mg/dL) and the H-TGL activity was very low (4.6 ± 4.5 μmol/h/mL). The H-TGL activity was also significantly correlated with the ratio of high density lipoprotein-2 to high density lipoprotein-3 cholesterol (r = 0.351, P < 0.001) in the entire group. The present study provided further evidence in favor of the hyptohesis that a decrease in H-TGL activity in hyperlipidemic patients with high levels of very low density lipoprotein (VLDL), such as type IIb, IV, and V cases, contributes to IDL accumulation, and suggests that H-TGL plays an important role in IDL metabolism, especially in hyperlipidemia associated with increased levels of VLDL.
  Metabolism.
• Article: Stimulation of the activity and mRNA level of hepatic triacylglycerol lipase by triiodothyronine in HepG2 cells

  Shuichi Nozaki, Iichiro Shimomura, Tohru Funahashi, Masakazu Menju, Masaharu Kubo, Yuji Matsuzawa
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  ABSTRACT: We have studied the effects of triiodothyronine (T3) on the production of hepatic triacylglycerol lipase (HTGL) in the human hepatocellular carcinoma cell line, HepG2, by measuring its activity and mRNA levels. The HTGL activity released into the medium by heparin, increased after the addition of T3 in a both time- (27% increase after 24 and 75% increase after 48 h) and dose-dependent manner (maximum activity with over 0.2 μg/ml of T3 in the medium). Messenger RNA levels of HTGL in cells incubated with T3 for 24 and 48 h were increased by 33% and 98% compared to those of the control. These results suggest that the production of HTGL may be regulated by thyroid hormone at the level of gene expression.
  Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1127(3):298-302.
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  Article: Localization of CD36 and scavenger receptor class A in human coronary arteries — a possible difference in the contribution of both receptors to plaque formation

  Yumiko Nakagawa-Toyama, Shizuya Yamashita, Jun-ichiro Miyagawa, Makoto Nishida, Shuichi Nozaki, Hiroyuki Nagaretani, Naohiko Sakai, Hisatoyo Hiraoka, Katsumi Yamamori, Tetsumi Yamane, Ken-ichi Hirano, Yuji Matsuzawa
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  ABSTRACT: CD36 and scavenger receptor class A types I and II (SR-AI/II) are major receptors for oxidized low density lipoproteins (OxLDL) expressed on macrophages. To elucidate the role of these two macrophage scavenger receptors in the development of coronary atherosclerosis, we examined the localization of CD36 and SR-AI/II in human coronary atherosclerotic lesions. Serial cryostat sections of 49 coronary arteries obtained from 43 autopsied cases were examined immunohistochemically. Regarding the relationship between the severity of atherosclerosis and immunoreactivities to CD36, there was almost no immunoreactivity to CD36 in regions with diffuse intimal thickening, while the expression of CD36 was accelerated in parallel with the progression of atherosclerosis. In contrast, SR-AI/II was expressed persistently from regions with diffuse intimal thickening to atherosclerotic plaques. We also clarified the differential distribution of CD36 and SR-AI/II in atheromatous plaques. Close to the luminal surface of the intima, macrophages were relatively small in size, contained lesser lipids, and expressed SR-AI/II more abundantly than CD36. In contrast, macrophages in the core region were larger in size, contained more lipids, were strongly positive for CD36 and showed a weaker immunoreactivity to SR-AI/II than those in the luminal surface of the intima. In conclusion, the expression of CD36 and SR-AI/II on macrophages may be regulated differently in the process of coronary atherogenesis.
  Atherosclerosis 156(2):297-305. · 3.79 Impact Factor