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Newly developed selective immunoinactivation assay revealed reduction in adipose triglyceride lipase activity in peripheral leucocytes from patients with idiopathic triglyceride deposit cardiomyovasculopathy.
Takagi, Atsuko; Ikeda, Yasuyuki; Kobayashi, Kunihisa; Kobayashi, Kazuhiro; Ikeda, Yoshihiko; Kozawa, Junji; Miyauchi, Hideyuki; Li, Ming; Hashimoto, Chikako; Hara, Yasuhiro; Yamaguchi, Satoshi; Suzuki, Akira; Toda, Tatsushi; Nagasaka, Hironori; Hirano, Ken-Ichi.
Afiliação
  • Takagi A; Laboratory of Cardiovascular Disease, Novel, Non-invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan; Department of Molecular Pharmacology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fu
  • Ikeda Y; Laboratory of Cardiovascular Disease, Novel, Non-invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan.
  • Kobayashi K; Department of Endocrinology and Diabetes Mellitus, Fukuoka University Chikushi Hospital, 1-1-1, Zokumyoin, Chikushino, Fukuoka 818-8502, Japan.
  • Kobayashi K; Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Hyogo 650-0017, Japan.
  • Ikeda Y; Department of Pathology, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan.
  • Kozawa J; Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0872, Japan.
  • Miyauchi H; Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
  • Li M; Laboratory of Cardiovascular Disease, Novel, Non-invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan.
  • Hashimoto C; Laboratory of Cardiovascular Disease, Novel, Non-invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan.
  • Hara Y; Laboratory of Cardiovascular Disease, Novel, Non-invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan.
  • Yamaguchi S; Laboratory of Cardiovascular Disease, Novel, Non-invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan.
  • Suzuki A; Laboratory of Cardiovascular Disease, Novel, Non-invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan.
  • Toda T; Department of Neurology, Graduate School of Medicine and Faculty of Medicine, Tokyo University, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
  • Nagasaka H; Department of Pediatrics, Takarazuka City Hospital, 4-5-1, Obama, Takarazuka, Hyogo 665-0827, Japan.
  • Hirano KI; Laboratory of Cardiovascular Disease, Novel, Non-invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan. Electronic address: khirano@cnt-osaka.com.
Biochem Biophys Res Commun ; 495(1): 646-651, 2018 01 01.
Article em En | MEDLINE | ID: mdl-29146190
Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare and newly identified disease among patients requiring cardiac transplantation. TGCV is characterized by cardiomyocyte steatosis and triglyceride (TG)-deposit atherosclerosis, resulting from the abnormal intracellular metabolism of TG. TGCV is classified into primary and idiopathic types. Primary TGCV carries ultra-rare genetic mutations in the adipose triglyceride lipase (ATGL), a rate-liming enzyme that hydrolyzes intracellular TG in adipose and non-adipose tissues. Idiopathic TGCV, first identified among autopsied individuals with diabetes mellitus (DM) with severe heart diseases, shows no ATGL mutations and its causes and underlying mechanisms are still unknown. TGCV is difficult to diagnose in daily clinics, thereby demanding feasible diagnostic procedures. We aimed to develop an assay to measure ATGL activity using peripheral leucocytes. Human his6-ATGL was expressed in COS1 cells, purified to homogeneity, and used to raise a polyclonal antibody neutralizing TG-hydrolyzing activity of ATGL. We developed a selective immunoinactivation assay (SIIA) for the quantitation of ATGL activity in cell lysates of leucocytes by the antibody neutralizing ATGL activities. ATGL activity was measured in 13 idiopathic TGCV patients, with two patients with primary TGCV as the negative control. Healthy (non-DM) and DM controls without heart diseases were also subjected. The developed SIIA assay revealed significant reduction in ATGL activity in leucocytes from patients with idiopathic TGCV who did not carry ATGL mutations as compared with non-DM and DM controls. Thus, ATGL in leucocytes may be an important biomarker for the diagnosis of TGCV and our assay may provide insights into pathophysiology and elucidate the underlying mechanism of TGCV and related disorders.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Técnicas Imunoenzimáticas / Leucócitos / Lipase / Cardiomiopatias Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Técnicas Imunoenzimáticas / Leucócitos / Lipase / Cardiomiopatias Idioma: En Ano de publicação: 2018 Tipo de documento: Article