Essential Amino Acid Starvation-Induced Oxidative Stress Causes DNA Damage and Apoptosis in Murine Osteoblast-like Cells

Intracellular nutrient metabolism, particularly the metabolism of essential amino acids (EAAs), is crucial for cellular functions, including energy production and redox homeostasis. An EAA deficiency can lead to cellular dysfunction and oxidative stress. This study explores the mechanisms underlying...

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Main Authors: Runbo Li, Hirohito Kato, Chihiro Fumimoto, Yurika Nakamura, Kimihiro Yoshimura, Emika Minagawa, Keiju Omatsu, Chizuko Ogata, Yoichiro Taguchi, Makoto Umeda
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/20/15314
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author Runbo Li
Hirohito Kato
Chihiro Fumimoto
Yurika Nakamura
Kimihiro Yoshimura
Emika Minagawa
Keiju Omatsu
Chizuko Ogata
Yoichiro Taguchi
Makoto Umeda
author_facet Runbo Li
Hirohito Kato
Chihiro Fumimoto
Yurika Nakamura
Kimihiro Yoshimura
Emika Minagawa
Keiju Omatsu
Chizuko Ogata
Yoichiro Taguchi
Makoto Umeda
author_sort Runbo Li
collection DOAJ
description Intracellular nutrient metabolism, particularly the metabolism of essential amino acids (EAAs), is crucial for cellular functions, including energy production and redox homeostasis. An EAA deficiency can lead to cellular dysfunction and oxidative stress. This study explores the mechanisms underlying cellular responses to EAA starvation, focusing on ROS-induced DNA damage and apoptosis. MC3T3-E1 cells were subjected to EAA starvation, and various assays were conducted to assess cell proliferation, survival, DNA damage, and apoptosis. The antioxidant N-acetylcysteine (NAC) was employed to block ROS formation and mitigate cellular damage. Gene expression and Western blot analyses were performed to elucidate molecular pathways. EAA starvation-induced ROS generation, DNA damage, and apoptosis in MC3T3-E1 cells. NAC administration effectively reduced DNA damage and apoptosis, highlighting the pivotal role of ROS in mediating these cellular responses during EAA deficiency. This study demonstrates that EAA starvation triggers ROS-mediated DNA damage and apoptosis, offering insights into the intricate interplay between nutrient deficiency, oxidative stress, and programmed cell death. NAC emerges as a potential therapeutic intervention to counteract these adverse effects.
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spelling doaj.art-3aaf594d10a84e06889ba44e9b4b714e2023-11-19T16:44:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124201531410.3390/ijms242015314Essential Amino Acid Starvation-Induced Oxidative Stress Causes DNA Damage and Apoptosis in Murine Osteoblast-like CellsRunbo Li0Hirohito Kato1Chihiro Fumimoto2Yurika Nakamura3Kimihiro Yoshimura4Emika Minagawa5Keiju Omatsu6Chizuko Ogata7Yoichiro Taguchi8Makoto Umeda9Department of Periodontology, Osaka Dental University, Hirakata, Osaka 573-1121, JapanDepartment of Periodontology, Osaka Dental University, Hirakata, Osaka 573-1121, JapanDepartment of Periodontology, Osaka Dental University, Hirakata, Osaka 573-1121, JapanDepartment of Periodontology, Osaka Dental University, Hirakata, Osaka 573-1121, JapanDepartment of Periodontology, Osaka Dental University, Hirakata, Osaka 573-1121, JapanDepartment of Periodontology, Osaka Dental University, Hirakata, Osaka 573-1121, JapanDepartment of Periodontology, Osaka Dental University, Hirakata, Osaka 573-1121, JapanDepartment of Periodontology, Osaka Dental University, Hirakata, Osaka 573-1121, JapanDepartment of Periodontology, Osaka Dental University, Hirakata, Osaka 573-1121, JapanDepartment of Periodontology, Osaka Dental University, Hirakata, Osaka 573-1121, JapanIntracellular nutrient metabolism, particularly the metabolism of essential amino acids (EAAs), is crucial for cellular functions, including energy production and redox homeostasis. An EAA deficiency can lead to cellular dysfunction and oxidative stress. This study explores the mechanisms underlying cellular responses to EAA starvation, focusing on ROS-induced DNA damage and apoptosis. MC3T3-E1 cells were subjected to EAA starvation, and various assays were conducted to assess cell proliferation, survival, DNA damage, and apoptosis. The antioxidant N-acetylcysteine (NAC) was employed to block ROS formation and mitigate cellular damage. Gene expression and Western blot analyses were performed to elucidate molecular pathways. EAA starvation-induced ROS generation, DNA damage, and apoptosis in MC3T3-E1 cells. NAC administration effectively reduced DNA damage and apoptosis, highlighting the pivotal role of ROS in mediating these cellular responses during EAA deficiency. This study demonstrates that EAA starvation triggers ROS-mediated DNA damage and apoptosis, offering insights into the intricate interplay between nutrient deficiency, oxidative stress, and programmed cell death. NAC emerges as a potential therapeutic intervention to counteract these adverse effects.https://www.mdpi.com/1422-0067/24/20/15314essential amino acidsapoptosisROSosteoblasts
spellingShingle Runbo Li
Hirohito Kato
Chihiro Fumimoto
Yurika Nakamura
Kimihiro Yoshimura
Emika Minagawa
Keiju Omatsu
Chizuko Ogata
Yoichiro Taguchi
Makoto Umeda
Essential Amino Acid Starvation-Induced Oxidative Stress Causes DNA Damage and Apoptosis in Murine Osteoblast-like Cells
International Journal of Molecular Sciences
essential amino acids
apoptosis
ROS
osteoblasts
title Essential Amino Acid Starvation-Induced Oxidative Stress Causes DNA Damage and Apoptosis in Murine Osteoblast-like Cells
title_full Essential Amino Acid Starvation-Induced Oxidative Stress Causes DNA Damage and Apoptosis in Murine Osteoblast-like Cells
title_fullStr Essential Amino Acid Starvation-Induced Oxidative Stress Causes DNA Damage and Apoptosis in Murine Osteoblast-like Cells
title_full_unstemmed Essential Amino Acid Starvation-Induced Oxidative Stress Causes DNA Damage and Apoptosis in Murine Osteoblast-like Cells
title_short Essential Amino Acid Starvation-Induced Oxidative Stress Causes DNA Damage and Apoptosis in Murine Osteoblast-like Cells
title_sort essential amino acid starvation induced oxidative stress causes dna damage and apoptosis in murine osteoblast like cells
topic essential amino acids
apoptosis
ROS
osteoblasts
url https://www.mdpi.com/1422-0067/24/20/15314
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