Induction of astrocyte metallothioneins (MTs) by zinc confers resistance against the acute cytotoxic effects of methylmercury on cell swelling, Na+ uptake, and K+ release

Michael Aschner, Dawn R. Conklin, Chang Ping Yao, Jeffrey W. Allen, Kim H. Tan

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Metallothionein (MT) proteins play an important role in the detoxification of heavy metals. Since methylmercury (MeHg) preferentially accumulates in astrocytes, we investigated the ability of the astrocyte- specific MT isoform, MT-I, to attenuate MeHg-induced cytotoxicity. Increased astrocytic MT expression was achieved by 24-h pretreatment of neonatal rat primary astrocyte cultures with 100 μM zinc (ZnSO4). Subsequently, the astrocytes were treated with MeHg (10 μM), and its toxic effects on cell volume, Na+ uptake, and K+ release were investigated and compared to cells treated with or without MeHg, but in the absence of Zn pretreatment. Pretreatment of astrocytes with Zn was associated with a 2.9-fold increase in MT protein levels (P < 0.02), and a 5.6-fold increase in MT mRNA levels (p < 0.002) compared to control astrocytes. Astrocytes expressing increased MT protein levels were resistant to MeHg-induced swelling. In isotonic buffer the effect of MeHg on swelling was abolished (p < 0.01) by 24-h Zn pretreatment, in such a way that volume profiles in these cells did not differ from controls. Zn-induced increased expression of MTs was also associated with significant attenuation of astrocytic Na+ uptake (p < 0.01) and Rb+ (a marker for K+) release (p < 0.001) in response to treatment with MeHg. These results demonstrate (1) that astrocytes can be induced to express high levels of MT proteins by pretreatment with Zn, and (2) that Zn confers resistance against the acute effect of MeHg on astrocytic swelling and the associated changes in ion (Na+ and K+) transport. Taken together, the data suggest that astrocytic MT induction offers effective cellular adaptation to MeHg cytotoxicity.

Original languageEnglish (US)
Pages (from-to)254-261
Number of pages8
JournalBrain Research
Volume813
Issue number2
DOIs
StatePublished - Dec 7 1998
Externally publishedYes

Fingerprint

Metallothionein
Astrocytes
Zinc
Proteins
Poisons
Heavy Metals
Cell Size
Buffers
Protein Isoforms
Ions
Messenger RNA

Keywords

  • Astrocytes
  • Cell swelling
  • In vitro
  • K
  • Methylmercury
  • Na
  • Rat

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Induction of astrocyte metallothioneins (MTs) by zinc confers resistance against the acute cytotoxic effects of methylmercury on cell swelling, Na+ uptake, and K+ release. / Aschner, Michael; Conklin, Dawn R.; Yao, Chang Ping; Allen, Jeffrey W.; Tan, Kim H.

In: Brain Research, Vol. 813, No. 2, 07.12.1998, p. 254-261.

Research output: Contribution to journalArticle

@article{78142fcec307465aac9ea331cb2ec0c7,
title = "Induction of astrocyte metallothioneins (MTs) by zinc confers resistance against the acute cytotoxic effects of methylmercury on cell swelling, Na+ uptake, and K+ release",
abstract = "Metallothionein (MT) proteins play an important role in the detoxification of heavy metals. Since methylmercury (MeHg) preferentially accumulates in astrocytes, we investigated the ability of the astrocyte- specific MT isoform, MT-I, to attenuate MeHg-induced cytotoxicity. Increased astrocytic MT expression was achieved by 24-h pretreatment of neonatal rat primary astrocyte cultures with 100 μM zinc (ZnSO4). Subsequently, the astrocytes were treated with MeHg (10 μM), and its toxic effects on cell volume, Na+ uptake, and K+ release were investigated and compared to cells treated with or without MeHg, but in the absence of Zn pretreatment. Pretreatment of astrocytes with Zn was associated with a 2.9-fold increase in MT protein levels (P < 0.02), and a 5.6-fold increase in MT mRNA levels (p < 0.002) compared to control astrocytes. Astrocytes expressing increased MT protein levels were resistant to MeHg-induced swelling. In isotonic buffer the effect of MeHg on swelling was abolished (p < 0.01) by 24-h Zn pretreatment, in such a way that volume profiles in these cells did not differ from controls. Zn-induced increased expression of MTs was also associated with significant attenuation of astrocytic Na+ uptake (p < 0.01) and Rb+ (a marker for K+) release (p < 0.001) in response to treatment with MeHg. These results demonstrate (1) that astrocytes can be induced to express high levels of MT proteins by pretreatment with Zn, and (2) that Zn confers resistance against the acute effect of MeHg on astrocytic swelling and the associated changes in ion (Na+ and K+) transport. Taken together, the data suggest that astrocytic MT induction offers effective cellular adaptation to MeHg cytotoxicity.",
keywords = "Astrocytes, Cell swelling, In vitro, K, Methylmercury, Na, Rat",
author = "Michael Aschner and Conklin, {Dawn R.} and Yao, {Chang Ping} and Allen, {Jeffrey W.} and Tan, {Kim H.}",
year = "1998",
month = "12",
day = "7",
doi = "10.1016/S0006-8993(98)00947-0",
language = "English (US)",
volume = "813",
pages = "254--261",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Induction of astrocyte metallothioneins (MTs) by zinc confers resistance against the acute cytotoxic effects of methylmercury on cell swelling, Na+ uptake, and K+ release

AU - Aschner, Michael

AU - Conklin, Dawn R.

AU - Yao, Chang Ping

AU - Allen, Jeffrey W.

AU - Tan, Kim H.

PY - 1998/12/7

Y1 - 1998/12/7

N2 - Metallothionein (MT) proteins play an important role in the detoxification of heavy metals. Since methylmercury (MeHg) preferentially accumulates in astrocytes, we investigated the ability of the astrocyte- specific MT isoform, MT-I, to attenuate MeHg-induced cytotoxicity. Increased astrocytic MT expression was achieved by 24-h pretreatment of neonatal rat primary astrocyte cultures with 100 μM zinc (ZnSO4). Subsequently, the astrocytes were treated with MeHg (10 μM), and its toxic effects on cell volume, Na+ uptake, and K+ release were investigated and compared to cells treated with or without MeHg, but in the absence of Zn pretreatment. Pretreatment of astrocytes with Zn was associated with a 2.9-fold increase in MT protein levels (P < 0.02), and a 5.6-fold increase in MT mRNA levels (p < 0.002) compared to control astrocytes. Astrocytes expressing increased MT protein levels were resistant to MeHg-induced swelling. In isotonic buffer the effect of MeHg on swelling was abolished (p < 0.01) by 24-h Zn pretreatment, in such a way that volume profiles in these cells did not differ from controls. Zn-induced increased expression of MTs was also associated with significant attenuation of astrocytic Na+ uptake (p < 0.01) and Rb+ (a marker for K+) release (p < 0.001) in response to treatment with MeHg. These results demonstrate (1) that astrocytes can be induced to express high levels of MT proteins by pretreatment with Zn, and (2) that Zn confers resistance against the acute effect of MeHg on astrocytic swelling and the associated changes in ion (Na+ and K+) transport. Taken together, the data suggest that astrocytic MT induction offers effective cellular adaptation to MeHg cytotoxicity.

AB - Metallothionein (MT) proteins play an important role in the detoxification of heavy metals. Since methylmercury (MeHg) preferentially accumulates in astrocytes, we investigated the ability of the astrocyte- specific MT isoform, MT-I, to attenuate MeHg-induced cytotoxicity. Increased astrocytic MT expression was achieved by 24-h pretreatment of neonatal rat primary astrocyte cultures with 100 μM zinc (ZnSO4). Subsequently, the astrocytes were treated with MeHg (10 μM), and its toxic effects on cell volume, Na+ uptake, and K+ release were investigated and compared to cells treated with or without MeHg, but in the absence of Zn pretreatment. Pretreatment of astrocytes with Zn was associated with a 2.9-fold increase in MT protein levels (P < 0.02), and a 5.6-fold increase in MT mRNA levels (p < 0.002) compared to control astrocytes. Astrocytes expressing increased MT protein levels were resistant to MeHg-induced swelling. In isotonic buffer the effect of MeHg on swelling was abolished (p < 0.01) by 24-h Zn pretreatment, in such a way that volume profiles in these cells did not differ from controls. Zn-induced increased expression of MTs was also associated with significant attenuation of astrocytic Na+ uptake (p < 0.01) and Rb+ (a marker for K+) release (p < 0.001) in response to treatment with MeHg. These results demonstrate (1) that astrocytes can be induced to express high levels of MT proteins by pretreatment with Zn, and (2) that Zn confers resistance against the acute effect of MeHg on astrocytic swelling and the associated changes in ion (Na+ and K+) transport. Taken together, the data suggest that astrocytic MT induction offers effective cellular adaptation to MeHg cytotoxicity.

KW - Astrocytes

KW - Cell swelling

KW - In vitro

KW - K

KW - Methylmercury

KW - Na

KW - Rat

UR - http://www.scopus.com/inward/record.url?scp=0032495227&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032495227&partnerID=8YFLogxK

U2 - 10.1016/S0006-8993(98)00947-0

DO - 10.1016/S0006-8993(98)00947-0

M3 - Article

VL - 813

SP - 254

EP - 261

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 2

ER -