Antiischemic effects of SB203580 are mediated through the inhibition of p38α mitogen-activated protein kinase: Evidence from ectopic expression of an inhibition-resistant kinase

Jody L. Martin; Metin Avkiran; Roy A. Quinlan; Philip Cohen; Michael S. Marber

doi:10.1161/hh2101.099504

Antiischemic effects of SB203580 are mediated through the inhibition of p38α mitogen-activated protein kinase: Evidence from ectopic expression of an inhibition-resistant kinase

Jody L. Martin, Metin Avkiran, Roy A. Quinlan, Philip Cohen, Michael S. Marber

Research output: Contribution to journal › Article › peer-review

68 Citations (Scopus)

Abstract

The aim of the present study was to determine whether the attenuation of myocardial ischemic injury by SB203580 is due to the inhibition of p38 mitogen-activated protein kinase (MAPK) or to other documented nonspecific effects of the drug. We made adenoviral vectors encoding the α isoform of p38 MAPK with or without site-directed mutations to prevent SB203580 binding and inhibition. In embryonal rat heart-derived cells and adult rat cardiocytes expressing wild-type p38α MAPK, injury was reduced significantly by SB203580 present during simulated ischemia. In contrast, SB203580 did not protect cells expressing the SB203580-resistant form of p38α MAPK. These observations suggest that SB203580-mediated protection depends on the inhibition of p38α MAPK.

Original language	English
Pages (from-to)	750-752
Number of pages	3
Journal	Circulation Research
Volume	89
Issue number	9
DOIs	https://doi.org/10.1161/hh2101.099504
Publication status	Published - 26 Oct 2001

Keywords

Isolated cells
p38 mitogen-activated protein kinase
Preconditioning
SB203580
Signaling

ASJC Scopus subject areas

Physiology
Cardiology and Cardiovascular Medicine

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title = "Antiischemic effects of SB203580 are mediated through the inhibition of p38α mitogen-activated protein kinase: Evidence from ectopic expression of an inhibition-resistant kinase",

abstract = "The aim of the present study was to determine whether the attenuation of myocardial ischemic injury by SB203580 is due to the inhibition of p38 mitogen-activated protein kinase (MAPK) or to other documented nonspecific effects of the drug. We made adenoviral vectors encoding the α isoform of p38 MAPK with or without site-directed mutations to prevent SB203580 binding and inhibition. In embryonal rat heart-derived cells and adult rat cardiocytes expressing wild-type p38α MAPK, injury was reduced significantly by SB203580 present during simulated ischemia. In contrast, SB203580 did not protect cells expressing the SB203580-resistant form of p38α MAPK. These observations suggest that SB203580-mediated protection depends on the inhibition of p38α MAPK.",

keywords = "Isolated cells, p38 mitogen-activated protein kinase, Preconditioning, SB203580, Signaling",

author = "Martin, {Jody L.} and Metin Avkiran and Quinlan, {Roy A.} and Philip Cohen and Marber, {Michael S.}",

year = "2001",

month = oct,

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doi = "10.1161/hh2101.099504",

language = "English",

volume = "89",

pages = "750--752",

journal = "Circulation Research",

issn = "0009-7330",

publisher = "Lippincott Williams and Wilkins",

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Antiischemic effects of SB203580 are mediated through the inhibition of p38α mitogen-activated protein kinase: Evidence from ectopic expression of an inhibition-resistant kinase. / Martin, Jody L.; Avkiran, Metin; Quinlan, Roy A. et al.
In: Circulation Research, Vol. 89, No. 9, 26.10.2001, p. 750-752.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Antiischemic effects of SB203580 are mediated through the inhibition of p38α mitogen-activated protein kinase

T2 - Evidence from ectopic expression of an inhibition-resistant kinase

AU - Martin, Jody L.

AU - Avkiran, Metin

AU - Quinlan, Roy A.

AU - Cohen, Philip

AU - Marber, Michael S.

PY - 2001/10/26

Y1 - 2001/10/26

N2 - The aim of the present study was to determine whether the attenuation of myocardial ischemic injury by SB203580 is due to the inhibition of p38 mitogen-activated protein kinase (MAPK) or to other documented nonspecific effects of the drug. We made adenoviral vectors encoding the α isoform of p38 MAPK with or without site-directed mutations to prevent SB203580 binding and inhibition. In embryonal rat heart-derived cells and adult rat cardiocytes expressing wild-type p38α MAPK, injury was reduced significantly by SB203580 present during simulated ischemia. In contrast, SB203580 did not protect cells expressing the SB203580-resistant form of p38α MAPK. These observations suggest that SB203580-mediated protection depends on the inhibition of p38α MAPK.

AB - The aim of the present study was to determine whether the attenuation of myocardial ischemic injury by SB203580 is due to the inhibition of p38 mitogen-activated protein kinase (MAPK) or to other documented nonspecific effects of the drug. We made adenoviral vectors encoding the α isoform of p38 MAPK with or without site-directed mutations to prevent SB203580 binding and inhibition. In embryonal rat heart-derived cells and adult rat cardiocytes expressing wild-type p38α MAPK, injury was reduced significantly by SB203580 present during simulated ischemia. In contrast, SB203580 did not protect cells expressing the SB203580-resistant form of p38α MAPK. These observations suggest that SB203580-mediated protection depends on the inhibition of p38α MAPK.

KW - Isolated cells

KW - p38 mitogen-activated protein kinase

KW - Preconditioning

KW - SB203580

KW - Signaling

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DO - 10.1161/hh2101.099504

M3 - Article

C2 - 11679403

AN - SCOPUS:0035955751

SN - 0009-7330

VL - 89

SP - 750

EP - 752

JO - Circulation Research

JF - Circulation Research

IS - 9

ER -

Antiischemic effects of SB203580 are mediated through the inhibition of p38α mitogen-activated protein kinase: Evidence from ectopic expression of an inhibition-resistant kinase

Abstract

Keywords

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