skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide

Abstract

Highlights: • PTEN is S-sulfhydrated endogenously in SH-SY5Y human neuroblastoma cells. • Preventing this modification by knocking down CBS renders PTEN sensitive to NO. • pAkt levels are increased significantly in CBS siRNA-transfected cells. • H{sub 2}S functions as an endogenous regulator of PTEN in neuronal cells. - Abstract: Hydrogen sulfide (H{sub 2}S) is a gaseous regulatory factor produced by several enzymes, and plays a pivotal role in processes such as proliferation or vasodilation. Recent reports demonstrated the physiological and pathophysiological functions of H{sub 2}S in neurons. PTEN is a target of nitric oxide (NO) or hydrogen peroxide, and the oxidative modification of cysteine (Cys) residue(s) attenuates its enzymatic activity. In the present study, we assessed the effect of H{sub 2}S on the direct modification of PTEN and the resulting downstream signaling. A modified biotin switch assay in SH-SY5Y human neuroblastoma cells revealed that PTEN is S-sulfhydrated endogenously. Subsequently, site-directed mutagenesis demonstrated that both Cys71 and Cys124 in PTEN are targets for S-sulfhydration. Further, the knockdown of cystathionine β-synthetase (CBS) using siRNA decreased this modification in a manner that was correlated to amount of H{sub 2}S. PTEN was more sensitive to NO under these conditions. These results suggest that themore » endogenous S-sulfhydration of PTEN via CBS/H{sub 2}S plays a role in preventing the S-nitrosylation that would inhibition its enzymatic activity under physiological conditions.« less

Authors:
; ;
Publication Date:
OSTI Identifier:
22416878
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 456; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOTIN; CELL PROLIFERATION; CYSTEINE; HUMAN POPULATIONS; HYDROGEN PEROXIDE; HYDROGEN SULFIDES; LIGASES; MODIFICATIONS; MUTAGENESIS; NERVE CELLS; NITRIC OXIDE; OXIDATION; RESIDUES; VASODILATION

Citation Formats

Ohno, Kazuki, Okuda, Kosaku, and Uehara, Takashi, E-mail: uehara@pharm.okayama-u.ac.jp. Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2014.11.066.
Ohno, Kazuki, Okuda, Kosaku, & Uehara, Takashi, E-mail: uehara@pharm.okayama-u.ac.jp. Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide. United States. doi:10.1016/J.BBRC.2014.11.066.
Ohno, Kazuki, Okuda, Kosaku, and Uehara, Takashi, E-mail: uehara@pharm.okayama-u.ac.jp. Fri . "Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide". United States. doi:10.1016/J.BBRC.2014.11.066.
@article{osti_22416878,
title = {Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide},
author = {Ohno, Kazuki and Okuda, Kosaku and Uehara, Takashi, E-mail: uehara@pharm.okayama-u.ac.jp},
abstractNote = {Highlights: • PTEN is S-sulfhydrated endogenously in SH-SY5Y human neuroblastoma cells. • Preventing this modification by knocking down CBS renders PTEN sensitive to NO. • pAkt levels are increased significantly in CBS siRNA-transfected cells. • H{sub 2}S functions as an endogenous regulator of PTEN in neuronal cells. - Abstract: Hydrogen sulfide (H{sub 2}S) is a gaseous regulatory factor produced by several enzymes, and plays a pivotal role in processes such as proliferation or vasodilation. Recent reports demonstrated the physiological and pathophysiological functions of H{sub 2}S in neurons. PTEN is a target of nitric oxide (NO) or hydrogen peroxide, and the oxidative modification of cysteine (Cys) residue(s) attenuates its enzymatic activity. In the present study, we assessed the effect of H{sub 2}S on the direct modification of PTEN and the resulting downstream signaling. A modified biotin switch assay in SH-SY5Y human neuroblastoma cells revealed that PTEN is S-sulfhydrated endogenously. Subsequently, site-directed mutagenesis demonstrated that both Cys71 and Cys124 in PTEN are targets for S-sulfhydration. Further, the knockdown of cystathionine β-synthetase (CBS) using siRNA decreased this modification in a manner that was correlated to amount of H{sub 2}S. PTEN was more sensitive to NO under these conditions. These results suggest that the endogenous S-sulfhydration of PTEN via CBS/H{sub 2}S plays a role in preventing the S-nitrosylation that would inhibition its enzymatic activity under physiological conditions.},
doi = {10.1016/J.BBRC.2014.11.066},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 456,
place = {United States},
year = {Fri Jan 02 00:00:00 EST 2015},
month = {Fri Jan 02 00:00:00 EST 2015}
}