A Novel Role for Glyceraldehyde-3-Phosphate Dehydrogenase and Monoamine Oxidase B Cascade in Ethanol-Induced Cellular Damage

Xiao Ming Ou; Craig A. Stockmeier; Herbert Y. Meltzer; James C. Overholser; George J. Jurjus; Lesa Dieter; Kevin Chen; Deyin Lu; Chandra Johnson; Moussa B H Youdim; Mark C. Austin; Jia Luo; Akira Sawa; Warren May; Jean C. Shih

doi:10.1016/j.biopsych.2009.10.032

A Novel Role for Glyceraldehyde-3-Phosphate Dehydrogenase and Monoamine Oxidase B Cascade in Ethanol-Induced Cellular Damage

Xiao Ming Ou^*, Craig A. Stockmeier, Herbert Y. Meltzer, James C. Overholser, George J. Jurjus, Lesa Dieter, Kevin Chen, Deyin Lu, Chandra Johnson, Moussa B H Youdim, Mark C. Austin, Jia Luo, Akira Sawa, Warren May, Jean C. Shih

^*Corresponding author for this work

Psychiatry and Behavioral Sciences

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

51 Scopus citations

Abstract

Background: Alcoholism is a major psychiatric condition at least partly associated with ethanol (EtOH)-induced cell damage. Although brain cell loss has been reported in subjects with alcoholism, the molecular mechanism is unclear. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and monoamine oxidase B (MAO B) reportedly play a role in cellular dysfunction under stressful conditions and might contribute to EtOH-induced cell damage. Methods: Expression of GAPDH and MAO B protein was studied in human glioblastoma and neuroblastoma cell lines exposed to physiological concentrations of EtOH. Expression of these proteins was also examined in the prefrontal cortex from human subjects with alcohol dependence and in rats fed with an EtOH diet. Coimmunoprecipitation, subcellular fractionation, and luciferase assay were used to address nuclear GAPDH-mediated MAO B activation. To test the effects of inactivation, RNA interference and pharmacological intervention were used, and cell damage was assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP Nick End Labeling (TUNEL) and hydrogen peroxide measurements. Results: Ethanol significantly increases levels of GAPDH, especially nuclear GAPDH, and MAO B in neuronal cells as well as in human and rat brains. Nuclear GAPDH interacts with the transcriptional activator, transforming growth factor-β-inducible early gene 2 (TIEG2), and augments TIEG2-mediated MAO B transactivation, which results in cell damage in neuronal cells exposed to EtOH. Knockdown expression of GAPDH or treatment with MAO B inhibitors selegiline (deprenyl) and rasagiline (Azilect) can block this cascade. Conclusions: Ethanol-elicited nuclear GAPDH augments TIEG2-mediated MAO B, which might play a role in brain damage in subjects with alcoholism. Compounds that block this cascade are potential candidates for therapeutic strategies.

Original language	English (US)
Pages (from-to)	855-863
Number of pages	9
Journal	Biological psychiatry
Volume	67
Issue number	9
DOIs	https://doi.org/10.1016/j.biopsych.2009.10.032
State	Published - May 1 2010

Funding

This study was supported by Public Health Service Grants P20 RR 017701 (CAS) and MH67996 (CAS), a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award (X-MO), an Intramural Research Support grant from the University of Mississippi Medical Center (X-MO), MH-084018 (AS), MH-069853 (AS), grants from Stanley (AS), Cure HD Initiative (AS), High Q (AS), S-R (AS), NARSAD (AS), National Institute of Mental Health Grant R37 MH39085 (Merit Award; JCS), RO1 MH67968 (JCS) and Boyd and Elsie Welin Professor (JCS). We acknowledge the invaluable contributions made by the families consenting to donate brain tissue and to be interviewed. We also thank the Cuyahoga County Coroner and staff, Cleveland, Ohio, for their assistance. We appreciate Dr. Raul Urrutia for providing us with the TIEG2-pcDNA3.1 expression vector and Dr. Gouri Mahajan for preparation of tissue samples. In addition, we thank Indiana University Alcohol Research Center for providing us with EtOH-preferring Wistar rats; this Alcohol Research Center is supported by R24 Alcohol Research Resource Award Grant (R24 AA015512-02) from the National Institute on Alcohol Abuse and Alcoholism.

Keywords

Alcoholism
ethanol-induced brain cell dysfunction
glyceraldehyde-3-phosphate dehydrogenase
human brain tissues
monoamine oxidase B
rats fed with an ethanol diet

ASJC Scopus subject areas

Biological Psychiatry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.biopsych.2009.10.032

Cite this

Ou, X. M., Stockmeier, C. A., Meltzer, H. Y., Overholser, J. C., Jurjus, G. J., Dieter, L., Chen, K., Lu, D., Johnson, C., Youdim, M. B. H., Austin, M. C., Luo, J., Sawa, A., May, W., & Shih, J. C. (2010). A Novel Role for Glyceraldehyde-3-Phosphate Dehydrogenase and Monoamine Oxidase B Cascade in Ethanol-Induced Cellular Damage. Biological psychiatry, 67(9), 855-863. https://doi.org/10.1016/j.biopsych.2009.10.032

@article{87089e591d7f4120832dd45e33880aa8,

title = "A Novel Role for Glyceraldehyde-3-Phosphate Dehydrogenase and Monoamine Oxidase B Cascade in Ethanol-Induced Cellular Damage",

abstract = "Background: Alcoholism is a major psychiatric condition at least partly associated with ethanol (EtOH)-induced cell damage. Although brain cell loss has been reported in subjects with alcoholism, the molecular mechanism is unclear. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and monoamine oxidase B (MAO B) reportedly play a role in cellular dysfunction under stressful conditions and might contribute to EtOH-induced cell damage. Methods: Expression of GAPDH and MAO B protein was studied in human glioblastoma and neuroblastoma cell lines exposed to physiological concentrations of EtOH. Expression of these proteins was also examined in the prefrontal cortex from human subjects with alcohol dependence and in rats fed with an EtOH diet. Coimmunoprecipitation, subcellular fractionation, and luciferase assay were used to address nuclear GAPDH-mediated MAO B activation. To test the effects of inactivation, RNA interference and pharmacological intervention were used, and cell damage was assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP Nick End Labeling (TUNEL) and hydrogen peroxide measurements. Results: Ethanol significantly increases levels of GAPDH, especially nuclear GAPDH, and MAO B in neuronal cells as well as in human and rat brains. Nuclear GAPDH interacts with the transcriptional activator, transforming growth factor-β-inducible early gene 2 (TIEG2), and augments TIEG2-mediated MAO B transactivation, which results in cell damage in neuronal cells exposed to EtOH. Knockdown expression of GAPDH or treatment with MAO B inhibitors selegiline (deprenyl) and rasagiline (Azilect) can block this cascade. Conclusions: Ethanol-elicited nuclear GAPDH augments TIEG2-mediated MAO B, which might play a role in brain damage in subjects with alcoholism. Compounds that block this cascade are potential candidates for therapeutic strategies.",

keywords = "Alcoholism, ethanol-induced brain cell dysfunction, glyceraldehyde-3-phosphate dehydrogenase, human brain tissues, monoamine oxidase B, rats fed with an ethanol diet",

author = "Ou, \{Xiao Ming\} and Stockmeier, \{Craig A.\} and Meltzer, \{Herbert Y.\} and Overholser, \{James C.\} and Jurjus, \{George J.\} and Lesa Dieter and Kevin Chen and Deyin Lu and Chandra Johnson and Youdim, \{Moussa B H\} and Austin, \{Mark C.\} and Jia Luo and Akira Sawa and Warren May and Shih, \{Jean C.\}",

note = "Funding Information: This study was supported by Public Health Service Grants P20 RR 017701 (CAS) and MH67996 (CAS), a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award (X-MO), an Intramural Research Support grant from the University of Mississippi Medical Center (X-MO), MH-084018 (AS), MH-069853 (AS), grants from Stanley (AS), Cure HD Initiative (AS), High Q (AS), S-R (AS), NARSAD (AS), National Institute of Mental Health Grant R37 MH39085 (Merit Award; JCS), RO1 MH67968 (JCS) and Boyd and Elsie Welin Professor (JCS). We acknowledge the invaluable contributions made by the families consenting to donate brain tissue and to be interviewed. We also thank the Cuyahoga County Coroner and staff, Cleveland, Ohio, for their assistance. We appreciate Dr. Raul Urrutia for providing us with the TIEG2-pcDNA3.1 expression vector and Dr. Gouri Mahajan for preparation of tissue samples. In addition, we thank Indiana University Alcohol Research Center for providing us with EtOH-preferring Wistar rats; this Alcohol Research Center is supported by R24 Alcohol Research Resource Award Grant (R24 AA015512-02) from the National Institute on Alcohol Abuse and Alcoholism. ",

year = "2010",

month = may,

day = "1",

doi = "10.1016/j.biopsych.2009.10.032",

language = "English (US)",

volume = "67",

pages = "855--863",

journal = "Biological psychiatry",

issn = "0006-3223",

publisher = "Elsevier Inc.",

number = "9",

}

Ou, XM, Stockmeier, CA, Meltzer, HY, Overholser, JC, Jurjus, GJ, Dieter, L, Chen, K, Lu, D, Johnson, C, Youdim, MBH, Austin, MC, Luo, J, Sawa, A, May, W & Shih, JC 2010, 'A Novel Role for Glyceraldehyde-3-Phosphate Dehydrogenase and Monoamine Oxidase B Cascade in Ethanol-Induced Cellular Damage', Biological psychiatry, vol. 67, no. 9, pp. 855-863. https://doi.org/10.1016/j.biopsych.2009.10.032

TY - JOUR

T1 - A Novel Role for Glyceraldehyde-3-Phosphate Dehydrogenase and Monoamine Oxidase B Cascade in Ethanol-Induced Cellular Damage

AU - Ou, Xiao Ming

AU - Stockmeier, Craig A.

AU - Meltzer, Herbert Y.

AU - Overholser, James C.

AU - Jurjus, George J.

AU - Dieter, Lesa

AU - Chen, Kevin

AU - Lu, Deyin

AU - Johnson, Chandra

AU - Youdim, Moussa B H

AU - Austin, Mark C.

AU - Luo, Jia

AU - Sawa, Akira

AU - May, Warren

AU - Shih, Jean C.

N1 - Funding Information: This study was supported by Public Health Service Grants P20 RR 017701 (CAS) and MH67996 (CAS), a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award (X-MO), an Intramural Research Support grant from the University of Mississippi Medical Center (X-MO), MH-084018 (AS), MH-069853 (AS), grants from Stanley (AS), Cure HD Initiative (AS), High Q (AS), S-R (AS), NARSAD (AS), National Institute of Mental Health Grant R37 MH39085 (Merit Award; JCS), RO1 MH67968 (JCS) and Boyd and Elsie Welin Professor (JCS). We acknowledge the invaluable contributions made by the families consenting to donate brain tissue and to be interviewed. We also thank the Cuyahoga County Coroner and staff, Cleveland, Ohio, for their assistance. We appreciate Dr. Raul Urrutia for providing us with the TIEG2-pcDNA3.1 expression vector and Dr. Gouri Mahajan for preparation of tissue samples. In addition, we thank Indiana University Alcohol Research Center for providing us with EtOH-preferring Wistar rats; this Alcohol Research Center is supported by R24 Alcohol Research Resource Award Grant (R24 AA015512-02) from the National Institute on Alcohol Abuse and Alcoholism.

PY - 2010/5/1

Y1 - 2010/5/1

N2 - Background: Alcoholism is a major psychiatric condition at least partly associated with ethanol (EtOH)-induced cell damage. Although brain cell loss has been reported in subjects with alcoholism, the molecular mechanism is unclear. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and monoamine oxidase B (MAO B) reportedly play a role in cellular dysfunction under stressful conditions and might contribute to EtOH-induced cell damage. Methods: Expression of GAPDH and MAO B protein was studied in human glioblastoma and neuroblastoma cell lines exposed to physiological concentrations of EtOH. Expression of these proteins was also examined in the prefrontal cortex from human subjects with alcohol dependence and in rats fed with an EtOH diet. Coimmunoprecipitation, subcellular fractionation, and luciferase assay were used to address nuclear GAPDH-mediated MAO B activation. To test the effects of inactivation, RNA interference and pharmacological intervention were used, and cell damage was assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP Nick End Labeling (TUNEL) and hydrogen peroxide measurements. Results: Ethanol significantly increases levels of GAPDH, especially nuclear GAPDH, and MAO B in neuronal cells as well as in human and rat brains. Nuclear GAPDH interacts with the transcriptional activator, transforming growth factor-β-inducible early gene 2 (TIEG2), and augments TIEG2-mediated MAO B transactivation, which results in cell damage in neuronal cells exposed to EtOH. Knockdown expression of GAPDH or treatment with MAO B inhibitors selegiline (deprenyl) and rasagiline (Azilect) can block this cascade. Conclusions: Ethanol-elicited nuclear GAPDH augments TIEG2-mediated MAO B, which might play a role in brain damage in subjects with alcoholism. Compounds that block this cascade are potential candidates for therapeutic strategies.

AB - Background: Alcoholism is a major psychiatric condition at least partly associated with ethanol (EtOH)-induced cell damage. Although brain cell loss has been reported in subjects with alcoholism, the molecular mechanism is unclear. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and monoamine oxidase B (MAO B) reportedly play a role in cellular dysfunction under stressful conditions and might contribute to EtOH-induced cell damage. Methods: Expression of GAPDH and MAO B protein was studied in human glioblastoma and neuroblastoma cell lines exposed to physiological concentrations of EtOH. Expression of these proteins was also examined in the prefrontal cortex from human subjects with alcohol dependence and in rats fed with an EtOH diet. Coimmunoprecipitation, subcellular fractionation, and luciferase assay were used to address nuclear GAPDH-mediated MAO B activation. To test the effects of inactivation, RNA interference and pharmacological intervention were used, and cell damage was assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP Nick End Labeling (TUNEL) and hydrogen peroxide measurements. Results: Ethanol significantly increases levels of GAPDH, especially nuclear GAPDH, and MAO B in neuronal cells as well as in human and rat brains. Nuclear GAPDH interacts with the transcriptional activator, transforming growth factor-β-inducible early gene 2 (TIEG2), and augments TIEG2-mediated MAO B transactivation, which results in cell damage in neuronal cells exposed to EtOH. Knockdown expression of GAPDH or treatment with MAO B inhibitors selegiline (deprenyl) and rasagiline (Azilect) can block this cascade. Conclusions: Ethanol-elicited nuclear GAPDH augments TIEG2-mediated MAO B, which might play a role in brain damage in subjects with alcoholism. Compounds that block this cascade are potential candidates for therapeutic strategies.

KW - Alcoholism

KW - ethanol-induced brain cell dysfunction

KW - glyceraldehyde-3-phosphate dehydrogenase

KW - human brain tissues

KW - monoamine oxidase B

KW - rats fed with an ethanol diet

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DO - 10.1016/j.biopsych.2009.10.032

M3 - Article

C2 - 20022592

AN - SCOPUS:77950367630

SN - 0006-3223

VL - 67

SP - 855

EP - 863

JO - Biological psychiatry

JF - Biological psychiatry

IS - 9

ER -

A Novel Role for Glyceraldehyde-3-Phosphate Dehydrogenase and Monoamine Oxidase B Cascade in Ethanol-Induced Cellular Damage

Abstract

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UN SDGs

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