Aldose reductase regulates TNF-α-induced cell signaling and apoptosis in vascular endothelial cells

Kota V. Ramana; Aruni Bhatnagar; Satish K. Srivastava

doi:10.1016/j.febslet.2004.06.046

Aldose reductase regulates TNF-α-induced cell signaling and apoptosis in vascular endothelial cells

Kota V. Ramana, Aruni Bhatnagar, Satish K. Srivastava

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

40 Scopus citations

Abstract

In this study, we examined the role of aldose reductase (AR) in regulating the cytotoxic effects of TNF-α on human umbilical vein endothelial cells. Inhibition of AR by sorbinil or tolrestat prevented TNF-α-induced increase in Bax and Bak and the downregulation of Bcl-2. Inhibition of AR abrogated AP-1 DNA binding activity and prevented the activation of caspase-3, JNK, and p38 MAPK in cells stimulated by TNF-α. Exposure to TNF-α also induced apoptotic cell death, which was attenuated by AR inhibition or antisense ablation. These observations suggest that AR is a critical regulator of TNF-α-induced apoptotic signaling in endothelial cells.

Original language	English (US)
Pages (from-to)	189-194
Number of pages	6
Journal	FEBS Letters
Volume	570
Issue number	1-3
DOIs	https://doi.org/10.1016/j.febslet.2004.06.046
State	Published - Jul 16 2004
Externally published	Yes

Keywords

AP-1
Aldose reductase
Apoptosis
Bcl-2
Endothelial cell
TNF-α

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2004.06.046

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@article{a4a97774921845819659359c873df7fc,

title = "Aldose reductase regulates TNF-α-induced cell signaling and apoptosis in vascular endothelial cells",

abstract = "In this study, we examined the role of aldose reductase (AR) in regulating the cytotoxic effects of TNF-α on human umbilical vein endothelial cells. Inhibition of AR by sorbinil or tolrestat prevented TNF-α-induced increase in Bax and Bak and the downregulation of Bcl-2. Inhibition of AR abrogated AP-1 DNA binding activity and prevented the activation of caspase-3, JNK, and p38 MAPK in cells stimulated by TNF-α. Exposure to TNF-α also induced apoptotic cell death, which was attenuated by AR inhibition or antisense ablation. These observations suggest that AR is a critical regulator of TNF-α-induced apoptotic signaling in endothelial cells.",

keywords = "AP-1, Aldose reductase, Apoptosis, Bcl-2, Endothelial cell, TNF-α",

author = "Ramana, {Kota V.} and Aruni Bhatnagar and Srivastava, {Satish K.}",

note = "Funding Information: This work was supported in part by NIH grants DK36118 and EY01677 (to S.K.S.) and HL55477 (to A.B.). Technical assistance by Mr. Shriram Srivastava is gratefully acknowledged.",

year = "2004",

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doi = "10.1016/j.febslet.2004.06.046",

language = "English (US)",

volume = "570",

pages = "189--194",

journal = "FEBS Letters",

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number = "1-3",

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T1 - Aldose reductase regulates TNF-α-induced cell signaling and apoptosis in vascular endothelial cells

AU - Ramana, Kota V.

AU - Bhatnagar, Aruni

AU - Srivastava, Satish K.

N1 - Funding Information: This work was supported in part by NIH grants DK36118 and EY01677 (to S.K.S.) and HL55477 (to A.B.). Technical assistance by Mr. Shriram Srivastava is gratefully acknowledged.

PY - 2004/7/16

Y1 - 2004/7/16

N2 - In this study, we examined the role of aldose reductase (AR) in regulating the cytotoxic effects of TNF-α on human umbilical vein endothelial cells. Inhibition of AR by sorbinil or tolrestat prevented TNF-α-induced increase in Bax and Bak and the downregulation of Bcl-2. Inhibition of AR abrogated AP-1 DNA binding activity and prevented the activation of caspase-3, JNK, and p38 MAPK in cells stimulated by TNF-α. Exposure to TNF-α also induced apoptotic cell death, which was attenuated by AR inhibition or antisense ablation. These observations suggest that AR is a critical regulator of TNF-α-induced apoptotic signaling in endothelial cells.

AB - In this study, we examined the role of aldose reductase (AR) in regulating the cytotoxic effects of TNF-α on human umbilical vein endothelial cells. Inhibition of AR by sorbinil or tolrestat prevented TNF-α-induced increase in Bax and Bak and the downregulation of Bcl-2. Inhibition of AR abrogated AP-1 DNA binding activity and prevented the activation of caspase-3, JNK, and p38 MAPK in cells stimulated by TNF-α. Exposure to TNF-α also induced apoptotic cell death, which was attenuated by AR inhibition or antisense ablation. These observations suggest that AR is a critical regulator of TNF-α-induced apoptotic signaling in endothelial cells.

KW - AP-1

KW - Aldose reductase

KW - Apoptosis

KW - Bcl-2

KW - Endothelial cell

KW - TNF-α

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JO - FEBS Letters

JF - FEBS Letters

IS - 1-3

ER -

Aldose reductase regulates TNF-α-induced cell signaling and apoptosis in vascular endothelial cells

Abstract

Keywords

ASJC Scopus subject areas

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