دورية أكاديمية
Effects of ML-236B (compactin) on sterol synthesis and low density lipoprotein receptor activities in fibroblasts of patients with homozygous familial hypercholesterolemia
| العنوان: | Effects of ML-236B (compactin) on sterol synthesis and low density lipoprotein receptor activities in fibroblasts of patients with homozygous familial hypercholesterolemia |
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| المؤلفون: | Haba Toshihiro, Mabuchi Hiroshi, Yoshimura Akira, Watanabe Akira, Wakasugi Takanobu, Tatami Ryozo, Ueda Kosei, Ueda Ryosei, Kametani Tomio, Koizumi Junji, Miyamoto Susumu, Takeda Ryoyu, Takeshita Haruo |
| بيانات النشر: | American Society for Clinical Investigation |
| سنة النشر: | 1981 |
| المجموعة: | Kanazawa University Repository for Academic Resources (KURA) / 金沢大学学術情報リポジトリ |
| الوصف: | 金沢大学大学院医学系研究科 ; We studied biochemical genetics of low density lipoprotein (LDL) receptor mutations in fibroblasts from six homozygous and five heterozygous patients with familial hypercholesterolemia (FH). Three of six homozygotes are receptor-negative type and the other three homozygotes are receptor-defective type. In the cells from three receptor-negative homozygotes, the receptor binding, internalization, and degradation of 125I-LDL were 0.5 ± 0.3 ng/mg protein (mean ± SEM), 14 ± 8 and 8 ± 6 ng/mg protein per 6 h (four normal cells; 44 ± 3, 386 ± 32, and 1,335 ± 214 ng/mg protein per 6 h), respectively. In the cells from three receptor-defective homozygotes, the receptor binding, internalization, and degradation of 12:5I-LDL were 6 ± 2, 29 ± 8, and 90 ± 32 ng/mg protein per 6 h, respectively. In these six homozygotes, two pairs of siblings are included. Two siblings in the same family were classified as receptor-negative and two siblings in another family were classified as receptor-defective. The receptor-negative phenotypes and the receptor-defective phenotypes bred true in individual families. The cells from five heterozygotes showed ~46% of the normal activities of receptor. ML-236B, competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), completely inhibited the incorporation of [14C]acetate into digitonin-precipitable sterols in fibroblasts from normal subjects and heterozygous and homozygous patients with FH with the concentration of 0.5 μg/ml. However, at 0.05 μg/ml of ML-236 B sterol synthesis in fibroblasts from homozygotes was not completely suppressed in contrast to normal and heterozygous cells. Moreover, after preincubation with 0.05 μg/ml of ML-236B for 24 h in medium containing lipoproteins, sterol synthesis in the cells from receptor-negative homozygote showed 75% of the initial activity compared with that of 25% without preincubation. In the cells from a normal subject and heterozygote, sterol synthesis was inhibited even after preincubation. These ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0021-9738 |
| العلاقة: | https://doi.org/10.1172/jci110184Test; https://kanazawa-u.repo.nii.ac.jp/?action=repository_uri&item_id=13192Test; http://hdl.handle.net/2297/7211Test; Journal of Clinical Investigation, 67(5), 1532-1540(1981-01-01); AA00695520; https://kanazawa-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=13192&item_no=1&attribute_id=26&file_no=1Test |
| الإتاحة: | https://doi.org/10.1172/jci110184Test http://hdl.handle.net/2297/7211Test https://kanazawa-u.repo.nii.ac.jp/?action=repository_uri&item_id=13192Test https://kanazawa-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=13192&item_no=1&attribute_id=26&file_no=1Test |
| رقم الانضمام: | edsbas.5BD0FB35 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00219738 |
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