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Modulations of the mTORC2-GATA3 axis by an isorhamnetin activated endosomal-lysosomal system of the J774.1 macrophage-like cell line.
Sakai, Maiko; Ohnishi, Kohta; Masuda, Masashi; Harumoto, Erika; Fukuda, Teppei; Ohnishi, Aika; Ishii, Shunsuke; Ohminami, Hirokazu; Yamanaka-Okumura, Hisami; Ohashi, Kazuto; Itakura, Eisuke; Horikawa, Kazuki; Yonemura, Shigenobu; Hara, Taichi; Taketani, Yutaka.
Afiliação
  • Sakai M; Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima 770-8503, Japan.
  • Ohnishi K; Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima 770-8503, Japan.
  • Masuda M; Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima 770-8503, Japan.
  • Harumoto E; Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima 770-8503, Japan.
  • Fukuda T; Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima 770-8503, Japan.
  • Ohnishi A; Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima 770-8503, Japan.
  • Ishii S; Department of Biology, Graduate School of Science and Engineering, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8555, Japan.
  • Ohminami H; Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima 770-8503, Japan.
  • Yamanaka-Okumura H; Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima 770-8503, Japan.
  • Ohashi K; Department of Food Science and Nutrition, Doshisha Women College of Liberal Arts, Teramachi-Nishi-iru, Imadegawa-Kamigyo-ku, Kyoto 602-0893, Japan.
  • Itakura E; Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-cho, Maebashi-shi, Gunma 371-8512, Japan.
  • Horikawa K; Department of Biology, Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8555, Japan.
  • Yonemura S; Department of Optical Imaging, Advanced Research Promotion Center, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima 770-8503, Japan.
  • Hara T; Department of Cell Biology, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima 770-8503, Japan.
  • Taketani Y; Laboratory for Ultrastructural Research, Riken Center for Biosystems Dynamics Research, 2-2-3 Minatojimaminami-machi, Chuo-ku, Kobe-shi, Hyogo 650-0047, Japan.
J Clin Biochem Nutr ; 75(1): 24-32, 2024 Jul.
Article em En | MEDLINE | ID: mdl-39070537
ABSTRACT
The endosomal-lysosomal system represents a crucial degradation pathway for various extracellular substances, and its dysfunction is linked to cardiovascular and neurodegenerative diseases. This degradation process involves multiple

steps:

(1) the uptake of extracellular molecules, (2) transport of cargos to lysosomes, and (3) digestion by lysosomal enzymes. While cellular uptake and lysosomal function are reportedly regulated by the mTORC1-TFEB axis, the key regulatory signal for cargo transport remains unclear. Notably, our previous study discovered that isorhamnetin, a dietary flavonoid, enhances endosomal-lysosomal proteolysis in the J774.1 cell line independently of the mTORC1-TFEB axis. This finding suggests the involvement of another signal in the mechanism of isorhamnetin. This study analyzes the molecular mechanism of isorhamnetin using transcriptome analysis and reveals that the transcription factor GATA3 plays a critical role in enhanced endosomal-lysosomal degradation. Our data also demonstrate that mTORC2 regulates GATA3 nuclear translocation, and the mTORC2-GATA3 axis alters endosomal formation and maturation, facilitating the efficient transport of cargos to lysosomes. This study suggests that the mTORC2-GATA3 axis might be a novel target for the degradation of abnormal substances.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: J Clin Biochem Nutr Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: J Clin Biochem Nutr Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Japão