Isoproterenol enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human embryonic kidney cells through death receptor 5 up-regulation

Young Woo Eom, Ha Yun Jung, Ji Eun Oh, Jun Won Lee, Min Soo Ahn, Young Jin Youn, Sung Gyun Ahn, Jang Young Kim, Seung Hwan Lee, Junghan Yoon, Byung Su Yoo

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Abstract

Background and Objectives: Chronic impairment of β-adrenergic receptor signaling increases cardiac apoptosis, hypertrophy and fibrosis. The aim of this study was to investigate whether isoproterenol (ISO), an agonist of the adrenergic receptor, can enhance tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human embryonic kidney (HEK) 293 cells. Materials and Methods: HEK 293 cells were treated with ISO and/or TRAIL for 24 hours. Cell viability was evaluated by microscopy and an established viability assay, and apoptotic cell death was analyzed by staining with fluorescein isothiocynate-annexin-V/propidium iodide (PI) and caspase activation. To confirm the mechanism of cell death induced by co-treatment with ISO and TRAIL, expression of TRAIL receptor 2 (death receptor 5, DR5) was evaluated by immunoblotting. Results: Although ISO or TRAIL treatment decreased HEK 293 cell viability by 13% and 17%, respectively, co-treatment with ISO and TRAIL resulted in a markedly higher death rate of 35% after 24 hours. Increases were evident in early apoptotic cells (i.e., annexin-V positive/PI negative; 19.4%), late apoptotic cells (i.e., annexin-V positive/PI positive; 6.3%) and dead cells (i.e., annexin-V negative/PI positive; 1.1%) when cells were co-treated with ISO and TRAIL, compared to cells treated with either ISO or TRAIL. In addition, marked increases of cleaved cas-3, cleaved poly (adenosine diphosphate-ribose) polymerase and DR5 were observed in HEK 293 cells co-treated with ISO and TRAIL. Conclusion: Treatments combining ISO with TRAIL may be responsible for death of HEK 293 cells through DR5 up-regulation. Activation of adrenergic receptors is responsible for the synergistic cell death observed with TRAIL.

Original languageEnglish
Pages (from-to)93-98
Number of pages6
JournalKorean Circulation Journal
Volume46
Issue number1
DOIs
Publication statusPublished - 2016 Jan

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TNF-Related Apoptosis-Inducing Ligand Receptors
Isoproterenol
Cell Death
Up-Regulation
Tumor Necrosis Factor-alpha
Apoptosis
Ligands
Kidney
Propidium
Annexin A5
Adrenergic Receptors
Cell Survival
Poly Adenosine Diphosphate Ribose
Adrenergic Agonists
Cardiomegaly
Caspases
Fluorescein
Immunoblotting
Microscopy
Fibrosis

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

@article{58ef60591e1a4320affc87c5ce97dc08,
title = "Isoproterenol enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human embryonic kidney cells through death receptor 5 up-regulation",
abstract = "Background and Objectives: Chronic impairment of β-adrenergic receptor signaling increases cardiac apoptosis, hypertrophy and fibrosis. The aim of this study was to investigate whether isoproterenol (ISO), an agonist of the adrenergic receptor, can enhance tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human embryonic kidney (HEK) 293 cells. Materials and Methods: HEK 293 cells were treated with ISO and/or TRAIL for 24 hours. Cell viability was evaluated by microscopy and an established viability assay, and apoptotic cell death was analyzed by staining with fluorescein isothiocynate-annexin-V/propidium iodide (PI) and caspase activation. To confirm the mechanism of cell death induced by co-treatment with ISO and TRAIL, expression of TRAIL receptor 2 (death receptor 5, DR5) was evaluated by immunoblotting. Results: Although ISO or TRAIL treatment decreased HEK 293 cell viability by 13{\%} and 17{\%}, respectively, co-treatment with ISO and TRAIL resulted in a markedly higher death rate of 35{\%} after 24 hours. Increases were evident in early apoptotic cells (i.e., annexin-V positive/PI negative; 19.4{\%}), late apoptotic cells (i.e., annexin-V positive/PI positive; 6.3{\%}) and dead cells (i.e., annexin-V negative/PI positive; 1.1{\%}) when cells were co-treated with ISO and TRAIL, compared to cells treated with either ISO or TRAIL. In addition, marked increases of cleaved cas-3, cleaved poly (adenosine diphosphate-ribose) polymerase and DR5 were observed in HEK 293 cells co-treated with ISO and TRAIL. Conclusion: Treatments combining ISO with TRAIL may be responsible for death of HEK 293 cells through DR5 up-regulation. Activation of adrenergic receptors is responsible for the synergistic cell death observed with TRAIL.",
author = "Eom, {Young Woo} and Jung, {Ha Yun} and Oh, {Ji Eun} and Lee, {Jun Won} and Ahn, {Min Soo} and Youn, {Young Jin} and Ahn, {Sung Gyun} and Kim, {Jang Young} and Lee, {Seung Hwan} and Junghan Yoon and Yoo, {Byung Su}",
year = "2016",
month = "1",
doi = "10.4070/kcj.2016.46.1.93",
language = "English",
volume = "46",
pages = "93--98",
journal = "Korean Circulation Journal",
issn = "1738-5520",
publisher = "Korean Society of Circulation",
number = "1",

}

TY - JOUR

T1 - Isoproterenol enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human embryonic kidney cells through death receptor 5 up-regulation

AU - Eom, Young Woo

AU - Jung, Ha Yun

AU - Oh, Ji Eun

AU - Lee, Jun Won

AU - Ahn, Min Soo

AU - Youn, Young Jin

AU - Ahn, Sung Gyun

AU - Kim, Jang Young

AU - Lee, Seung Hwan

AU - Yoon, Junghan

AU - Yoo, Byung Su

PY - 2016/1

Y1 - 2016/1

N2 - Background and Objectives: Chronic impairment of β-adrenergic receptor signaling increases cardiac apoptosis, hypertrophy and fibrosis. The aim of this study was to investigate whether isoproterenol (ISO), an agonist of the adrenergic receptor, can enhance tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human embryonic kidney (HEK) 293 cells. Materials and Methods: HEK 293 cells were treated with ISO and/or TRAIL for 24 hours. Cell viability was evaluated by microscopy and an established viability assay, and apoptotic cell death was analyzed by staining with fluorescein isothiocynate-annexin-V/propidium iodide (PI) and caspase activation. To confirm the mechanism of cell death induced by co-treatment with ISO and TRAIL, expression of TRAIL receptor 2 (death receptor 5, DR5) was evaluated by immunoblotting. Results: Although ISO or TRAIL treatment decreased HEK 293 cell viability by 13% and 17%, respectively, co-treatment with ISO and TRAIL resulted in a markedly higher death rate of 35% after 24 hours. Increases were evident in early apoptotic cells (i.e., annexin-V positive/PI negative; 19.4%), late apoptotic cells (i.e., annexin-V positive/PI positive; 6.3%) and dead cells (i.e., annexin-V negative/PI positive; 1.1%) when cells were co-treated with ISO and TRAIL, compared to cells treated with either ISO or TRAIL. In addition, marked increases of cleaved cas-3, cleaved poly (adenosine diphosphate-ribose) polymerase and DR5 were observed in HEK 293 cells co-treated with ISO and TRAIL. Conclusion: Treatments combining ISO with TRAIL may be responsible for death of HEK 293 cells through DR5 up-regulation. Activation of adrenergic receptors is responsible for the synergistic cell death observed with TRAIL.

AB - Background and Objectives: Chronic impairment of β-adrenergic receptor signaling increases cardiac apoptosis, hypertrophy and fibrosis. The aim of this study was to investigate whether isoproterenol (ISO), an agonist of the adrenergic receptor, can enhance tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human embryonic kidney (HEK) 293 cells. Materials and Methods: HEK 293 cells were treated with ISO and/or TRAIL for 24 hours. Cell viability was evaluated by microscopy and an established viability assay, and apoptotic cell death was analyzed by staining with fluorescein isothiocynate-annexin-V/propidium iodide (PI) and caspase activation. To confirm the mechanism of cell death induced by co-treatment with ISO and TRAIL, expression of TRAIL receptor 2 (death receptor 5, DR5) was evaluated by immunoblotting. Results: Although ISO or TRAIL treatment decreased HEK 293 cell viability by 13% and 17%, respectively, co-treatment with ISO and TRAIL resulted in a markedly higher death rate of 35% after 24 hours. Increases were evident in early apoptotic cells (i.e., annexin-V positive/PI negative; 19.4%), late apoptotic cells (i.e., annexin-V positive/PI positive; 6.3%) and dead cells (i.e., annexin-V negative/PI positive; 1.1%) when cells were co-treated with ISO and TRAIL, compared to cells treated with either ISO or TRAIL. In addition, marked increases of cleaved cas-3, cleaved poly (adenosine diphosphate-ribose) polymerase and DR5 were observed in HEK 293 cells co-treated with ISO and TRAIL. Conclusion: Treatments combining ISO with TRAIL may be responsible for death of HEK 293 cells through DR5 up-regulation. Activation of adrenergic receptors is responsible for the synergistic cell death observed with TRAIL.

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