年間 4 号発行
ISSN 印刷: 0731-8898
ISSN オンライン: 2162-6537
Indexed in
Autophagy is Required to Regulate Mitochondria Renewal, Cell Attachment, and All-trans–Retinoic Acid–Induced Differentiation in NB4 Acute Promyelocytic Leukemia Cells
要約
All-trans–retinoic acid (ATRA) is a potent inducer of cellular differentiation, growth arrest, and apoptosis as well as a front-line therapy for acute promyelocytic leukemia (APL). The present study provides evidence that induction of autophagy is required for ATRA to induce differentiation of APL (NB4) cells into granulocytes. ATRA treatment causes ~12-fold increase in the number of acidic vesicular organelles and induces marked up-regulation of LC3-II, autophagy-related 5 (ATG5), and Beclin-1. Transmission electron microscopy (TEM) revealed a decrease in mitochondria and ATRA-induced differentiation. To determine the role of autophagy in the differentiation of APL, we knocked down ATG5 in NB4 cells to find that ATRA-induced differentiation is significantly inhibited during ATG5 knock down in cells, indicating the role of autophagy in differentiation of APL. Further experiments revealed restriction of autophagy during ATRA-induced differentiation and inhibition of tissue transglutaminase 2 (TG2) and phospho–focal adhesion kinase (p-FAK), which are known to have roles in differentiation and cell attachment. We examined expression of Beclin-1 and B-cell lymphoma–2 (Bcl-2) and levels of mechanistic target of rapamycin (mTOR) after ATRA treatment. ATRA inhibits Bcl-2, up-regulates Beclin-1 expression, and reduces induction of mTOR activation/phosphorylation in NB4 cells. Our results reveal that autophagy has roles in regulation of differentiation, mitochondria elimination, and cell attachment during ATRA-induced APL differentiation.
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Alatshan Ahmad, Kovács Gergő E., Aladdin Azzam, Czimmerer Zsolt, Tar Krisztina, Benkő Szilvia, All-Trans Retinoic Acid Enhances both the Signaling for Priming and the Glycolysis for Activation of NLRP3 Inflammasome in Human Macrophage, Cells, 9, 7, 2020. Crossref
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Sencan Sevide, Tanriover Mine, Ulasli Mustafa, Karakas Didem, Ozpolat Bulent, UV radiation resistance-associated gene (UVRAG) promotes cell proliferation, migration, invasion by regulating cyclin-dependent kinases (CDK) and integrin-β/Src signaling in breast cancer cells, Molecular and Cellular Biochemistry, 476, 5, 2021. Crossref
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Lampis Silvia, Raieli Salvatore, Montemurro Luca, Bartolucci Damiano, Amadesi Camilla, Bortolotti Sonia, Angelucci Silvia, Scardovi Anna Lisa, Nieddu Giammario, Cerisoli Lucia, Paganelli Francesca, Valente Sabrina, Fischer Matthias, Martelli Alberto Maria, Pasquinelli Gianandrea, Pession Andrea, Hrelia Patrizia, Tonelli Roberto, The MYCN inhibitor BGA002 restores the retinoic acid response leading to differentiation or apoptosis by the mTOR block in MYCN-amplified neuroblastoma, Journal of Experimental & Clinical Cancer Research, 41, 1, 2022. Crossref