Translocation of HSP47 and generation of mitochondrial reactive oxygen species in human neuroblastoma SK-N-SH cells following electron and X-ray irradiation

Indo, Hiroko P.; Ito, Hiromu; Nakagawa, Keiichi; Chaiswing, Luksana; Majima, Hideyuki J.

doi:10.1016/j.abb.2021.108853

Cited by 4 publications

(3 citation statements)

References 34 publications

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“…Although overexpression of chaperones such as HSP47 is associated with ROS production [51], our observation in the secretions of IL-1β, IL-6, and TNFα induced by CALRmediated ROS elevation in NB was unprecedented to date. Of note, our findings are also consistent with reported increases in cellular ROS that often lead to secretion of chemokines and proinflammatory cytokines via activations of key factors such as MAPK, extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs), and NF-κB [40,52].…”

Section: Discussionmentioning

confidence: 79%

Calreticulin Expression Controls Cellular Redox, Stemness, and Radiosensitivity to Function as a Novel Adjuvant for Radiotherapy in Neuroblastoma

Chen

Chien

et al. 2023

Oxidative Medicine and Cellular Longevity

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Radiotherapy (RT) is currently only used in children with high-risk neuroblastoma (NB) due to concerns of long-term side effects as well as lack of effective adjuvant. Calreticulin (CALR) has served distinct physiological roles in cancer malignancies; nonetheless, impact of radiation on chaperones and molecular roles they play remains largely unknown. In present study, we systemically analyzed correlation between CALR and NB cells of different malignancies to investigate potential role of CALR in mediating radioresistance of NB. Our data revealed that more malignant NB cells are correlated to lower CALR expression, greater radioresistance, and elevated stemness as indicated by colony- and neurospheroid-forming abilities and vice versa. Of note, manipulating CALR expression in NB cells of varying endogenous CALR expression manifested changes in not only stemness but also radioresistant properties of those NB cells. Further, CALR overexpression resulted in greatly enhanced ROS and led to increased secretion of proinflammatory cytokines. Importantly, growth of NB tumors was significantly hampered by CALR overexpression and was synergistically ablated when RT was also administered. Collectively, our current study unraveled a new notion of utilizing CALR expression in malignant NB to diminish cancer stemness and mitigate radioresistance to achieve favorable therapeutic outcome for NB.

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Section: Discussionmentioning

confidence: 79%

Calreticulin Expression Controls Cellular Redox, Stemness, and Radiosensitivity to Function as a Novel Adjuvant for Radiotherapy in Neuroblastoma

Chen

Chien

et al. 2023

Oxidative Medicine and Cellular Longevity

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“…Our laboratory demonstrated that carboplatin resistant ovarian cancer cells have higher mitochondria function and H 2 O 2 production levels than the parental ovarian cells [ 40 ] while aggressive PCa tissues exhibited redox imbalances via ROS-mediated post-translational modifications of antioxidant enzymes [ 41 ]. Previous studies have shown that ROS are generated during RT [ 42 ]. Due to the fact that radiation can cause the production of H 2 O 2 , we generated our radioresistant cell line, Clone 695.…”

Section: Introductionmentioning

confidence: 99%

Hydrogen Peroxide Promotes the Production of Radiation-Derived EVs Containing Mitochondrial Proteins

Miller

Zhao

et al. 2022

Antioxidants

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In spite of extensive successes, cancer recurrence after radiation treatment (RT) remains one of the significant challenges in the cure of localized prostate cancer (PCa). This study focuses on elucidating a novel adaptive response to RT that could contribute to cancer recurrence. Here, we used PC3 cell line, an adenocarcinoma from a bone metastasis and radio-resistant clone 695 cell line, which survived after total radiation dose of 66 Gy (2 Gy × 33) and subsequently regrew in nude mice after exposure to fractionated radiation at 10 Gy (2 Gy × 5). Clone 695 cells not only showed an increase in surviving fraction post-radiation but also an increase in hydrogen peroxide (H2O2) production when compared to PC3 cells. At the single cell level, confocal microscope images coupled with IMARIS rendering software demonstrate an increase in mitochondrial mass and membrane potential in clone 695 cells. Utilizing the Seahorse XF96 instrument to investigate mitochondrial respiration, clone 695 cells demonstrated a higher basal Oxygen Consumption Rate (OCR), ATP-linked OCR, and proton leak compared to PC3 cells. The elevation of mitochondrial function in clone 695 cells is accompanied by an increase in mitochondrial H2O2 production. These data suggest that H2O2 could reprogram PCa’s mitochondrial homeostasis, which allows the cancer to survive and regrow after RT. Upon exposure to RT, in addition to ROS production, we found that RT induces the release of extracellular vesicles (EVs) from PC3 cells (p < 0.05). Importantly, adding H2O2 to PC3 cells promotes EVs production in a dose-dependent manner and pre-treatment with polyethylene glycol-Catalase mitigates H2O2-mediated EV production. Both RT-derived EVs and H2O2-derived EVs carried higher levels of mitochondrial antioxidant proteins including, Peroxiredoxin 3, Glutathione Peroxidase 4 as well as mitochondrial-associated oxidative phosphorylation proteins. Significantly, adding isolated functional mitochondria 24 h prior to RT shows a significant increase in surviving fractions of PC3 cells (p < 0.05). Together, our findings reveal that H2O2 promotes the production of EVs carrying mitochondrial proteins and that functional mitochondria enhance cancer survival after RT.

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“…Belli et al [22] Contents lists available at ScienceDirect Archives of Biochemistry and Biophysics journal homepage: www.elsevier.com/locate/yabbi https://doi.org/10.1016/j.abb.2021.109006 well described the importance of mitochondrial ultrastructure with a special focus on human oocytes related to several clinical conditions. Indo et al [23] demonstrated how HSP47 overexpression increases mitochondrial ROS production in neuroblastoma cells after X-ray irradiation.…”

mentioning

confidence: 99%

Mitochondrial involvement in the development and progression of diseases

Valacchi

Pecorelli

Toyokuni

2021

Archives of Biochemistry and Biophysics

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Translocation of HSP47 and generation of mitochondrial reactive oxygen species in human neuroblastoma SK-N-SH cells following electron and X-ray irradiation

Cited by 4 publications

References 34 publications

Calreticulin Expression Controls Cellular Redox, Stemness, and Radiosensitivity to Function as a Novel Adjuvant for Radiotherapy in Neuroblastoma

Calreticulin Expression Controls Cellular Redox, Stemness, and Radiosensitivity to Function as a Novel Adjuvant for Radiotherapy in Neuroblastoma

Hydrogen Peroxide Promotes the Production of Radiation-Derived EVs Containing Mitochondrial Proteins

Mitochondrial involvement in the development and progression of diseases

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