Nicotinamide N-methyltransferase increases complex I activity in SH-SY5Y cells via sirtuin 3

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Nicotinamide N-methyltransferase increases complex I activity in SH-SY5Y cells via sirtuin 3. / Liu, Karolina Y.; Mistry, Rakhee J.; Aguirre, Carlos A.; Fasouli, Eirini S.; Thomas, Martin G.; Klamt, Fábio; Ramsden, David B.; Parsons, Richard B.

In: Biochemical and Biophysical Research Communications, Vol. 467, No. 3, 20.11.2015, p. 491-496.

Research output: Contribution to journalArticlepeer-review

Harvard

Liu, KY, Mistry, RJ, Aguirre, CA, Fasouli, ES, Thomas, MG, Klamt, F, Ramsden, DB & Parsons, RB 2015, 'Nicotinamide N-methyltransferase increases complex I activity in SH-SY5Y cells via sirtuin 3', Biochemical and Biophysical Research Communications, vol. 467, no. 3, pp. 491-496. https://doi.org/10.1016/j.bbrc.2015.10.023

APA

Liu, K. Y., Mistry, R. J., Aguirre, C. A., Fasouli, E. S., Thomas, M. G., Klamt, F., Ramsden, D. B., & Parsons, R. B. (2015). Nicotinamide N-methyltransferase increases complex I activity in SH-SY5Y cells via sirtuin 3. Biochemical and Biophysical Research Communications, 467(3), 491-496. https://doi.org/10.1016/j.bbrc.2015.10.023

Vancouver

Author

Liu, Karolina Y. ; Mistry, Rakhee J. ; Aguirre, Carlos A. ; Fasouli, Eirini S. ; Thomas, Martin G. ; Klamt, Fábio ; Ramsden, David B. ; Parsons, Richard B. / Nicotinamide N-methyltransferase increases complex I activity in SH-SY5Y cells via sirtuin 3. In: Biochemical and Biophysical Research Communications. 2015 ; Vol. 467, No. 3. pp. 491-496.

Bibtex

@article{fd377e5b6f094610b0e5ebd87561544e,
title = "Nicotinamide N-methyltransferase increases complex I activity in SH-SY5Y cells via sirtuin 3",
abstract = "Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to 1-methylnicotinamide. We have previously shown that NNMT is significantly overexpressed in the brains of patients who have died of Parkinson's disease, and others have shown that NNMT is significantly overexpressed in a variety of diseases ranging from cancer to hepatic cirrhosis. In vitro overexpression has revealed many cytoprotective effects of NNMT, in particular increased complex I activity and ATP synthesis. Although this appears to be mediated by an increase in 1-methylnicotinamide production, the molecular mechanisms involved remain unclear. In the present study, we have investigated the role that sirtuins 1, 2 and 3, class III DNA deacetylase enzymes known to regulate mitochondrial energy production and cell cycle, have in mediating the effects of NNMT upon complex I activity. Expression of NNMT in SH-SY5Y human neuroblastoma cells, which have no endogenous expression of NNMT, significantly increased the expression of all three sirtuins. siRNA-mediated silencing of sirtuin 3 expression decreased complex I activity in NNMT-expressing SH-SY5Y cells to that observed in wild-type SH-SY5Y, and significantly reduced cellular ATP content also. These results demonstrate that sirtuin 3 is a key mediator of NNMT-induced complex I activity and ATP synthesis. These results further reinforce a central role for NNMT in the regulation of energy homeostasis and provide further mechanistic insight into the consequences of enhanced NNMT expression.",
keywords = "nicotinamide N-methyltransferase, Cancer, ATP, Bioenergetics, Complex I, Parkinson's disease",
author = "Liu, {Karolina Y.} and Mistry, {Rakhee J.} and Aguirre, {Carlos A.} and Fasouli, {Eirini S.} and Thomas, {Martin G.} and F{\'a}bio Klamt and Ramsden, {David B.} and Parsons, {Richard B.}",
year = "2015",
month = nov,
day = "20",
doi = "10.1016/j.bbrc.2015.10.023",
language = "English",
volume = "467",
pages = "491--496",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - Nicotinamide N-methyltransferase increases complex I activity in SH-SY5Y cells via sirtuin 3

AU - Liu, Karolina Y.

AU - Mistry, Rakhee J.

AU - Aguirre, Carlos A.

AU - Fasouli, Eirini S.

AU - Thomas, Martin G.

AU - Klamt, Fábio

AU - Ramsden, David B.

AU - Parsons, Richard B.

PY - 2015/11/20

Y1 - 2015/11/20

N2 - Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to 1-methylnicotinamide. We have previously shown that NNMT is significantly overexpressed in the brains of patients who have died of Parkinson's disease, and others have shown that NNMT is significantly overexpressed in a variety of diseases ranging from cancer to hepatic cirrhosis. In vitro overexpression has revealed many cytoprotective effects of NNMT, in particular increased complex I activity and ATP synthesis. Although this appears to be mediated by an increase in 1-methylnicotinamide production, the molecular mechanisms involved remain unclear. In the present study, we have investigated the role that sirtuins 1, 2 and 3, class III DNA deacetylase enzymes known to regulate mitochondrial energy production and cell cycle, have in mediating the effects of NNMT upon complex I activity. Expression of NNMT in SH-SY5Y human neuroblastoma cells, which have no endogenous expression of NNMT, significantly increased the expression of all three sirtuins. siRNA-mediated silencing of sirtuin 3 expression decreased complex I activity in NNMT-expressing SH-SY5Y cells to that observed in wild-type SH-SY5Y, and significantly reduced cellular ATP content also. These results demonstrate that sirtuin 3 is a key mediator of NNMT-induced complex I activity and ATP synthesis. These results further reinforce a central role for NNMT in the regulation of energy homeostasis and provide further mechanistic insight into the consequences of enhanced NNMT expression.

AB - Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to 1-methylnicotinamide. We have previously shown that NNMT is significantly overexpressed in the brains of patients who have died of Parkinson's disease, and others have shown that NNMT is significantly overexpressed in a variety of diseases ranging from cancer to hepatic cirrhosis. In vitro overexpression has revealed many cytoprotective effects of NNMT, in particular increased complex I activity and ATP synthesis. Although this appears to be mediated by an increase in 1-methylnicotinamide production, the molecular mechanisms involved remain unclear. In the present study, we have investigated the role that sirtuins 1, 2 and 3, class III DNA deacetylase enzymes known to regulate mitochondrial energy production and cell cycle, have in mediating the effects of NNMT upon complex I activity. Expression of NNMT in SH-SY5Y human neuroblastoma cells, which have no endogenous expression of NNMT, significantly increased the expression of all three sirtuins. siRNA-mediated silencing of sirtuin 3 expression decreased complex I activity in NNMT-expressing SH-SY5Y cells to that observed in wild-type SH-SY5Y, and significantly reduced cellular ATP content also. These results demonstrate that sirtuin 3 is a key mediator of NNMT-induced complex I activity and ATP synthesis. These results further reinforce a central role for NNMT in the regulation of energy homeostasis and provide further mechanistic insight into the consequences of enhanced NNMT expression.

KW - nicotinamide N-methyltransferase

KW - Cancer

KW - ATP

KW - Bioenergetics

KW - Complex I

KW - Parkinson's disease

U2 - 10.1016/j.bbrc.2015.10.023

DO - 10.1016/j.bbrc.2015.10.023

M3 - Article

VL - 467

SP - 491

EP - 496

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 3

ER -