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Pyrogallol-induced As4.1 juxtaglomerular cell death is attenuated by MAPK inhibitors via preventing GSH depletion

  • Organ Toxicity and Mechanisms
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Abstract

Pyrogallol (PG) induces apoptosis in several types of cells mediated by superoxide anion (O •−2 ). Here, we investigated the effects of PG and/or MAPK (MEK, JNK, and p38) inhibitors on the changes in cell growth, cell death, reactive oxygen species (ROS), and GSH levels in As4.1 juxtaglomerular (JG) cells. PG inhibited the growth of As4.1 cells. It also induced apoptosis and the loss of mitochondrial membrane potential (MMP; ΔΨm) and increased the level of p53 protein. Intracellular O •−2 level was increased in PG-treated As4.1 cells. PG also increased the number of GSH deleted cells in As4.1 cells. All the MAPK inhibitors significantly attenuated the growth inhibition and death mediated by PG. They decreased the levels of p53 protein and MMP (ΔΨm) loss in PG-treated As4.1 cells. They also reduced O •−2 level and GSH-depleted cell number in these cells. In conclusion, MAPK inhibitors attenuated As4.1 cell growth inhibition and death mediated by PG treatment. The changes in O •−2 and GSH levels by PG and/or MAPK inhibitors appeared to affect the growth and death of As4.1 cells.

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Abbreviations

PG:

Pyrogallol

ROS:

Reactive oxygen species

MAPK:

Mitogen-activated protein kinase

MEK:

MAP kinase or ERK kinase

ERK:

Extracellular signal-regulated kinase

JNK:

c-Jun N-terminal kinase

SOD:

Superoxide dismutase

MMP (ΔΨm):

Mitochondrial membrane potential

FBS:

Fetal bovine serum

FITC:

Fluorescein isothiocyanate

H2DCFDA:

2′,7′-Dichlorodihydrofluorescein diacetate

DHE:

Dihydroethidium

GSH:

Glutathione

CMFDA:

5-Chloromethylfluorescein diacetate

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

PI:

Propidium iodide

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Acknowledgments

This research was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs and Republic of Korea (A084194).

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Authors and Affiliations

  1. Department of Physiology, Medical School, Chonbuk National University, JeonJu, 561-180, Republic of Korea

    Yong Hwan Han & Woo Hyun Park

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  1. Yong Hwan Han
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  2. Woo Hyun Park
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Correspondence to Woo Hyun Park.

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Han, Y.H., Park, W.H. Pyrogallol-induced As4.1 juxtaglomerular cell death is attenuated by MAPK inhibitors via preventing GSH depletion. Arch Toxicol 84, 631–640 (2010). https://doi.org/10.1007/s00204-010-0526-8

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  • DOI: https://doi.org/10.1007/s00204-010-0526-8

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