S-Propargyl-Cysteine Ameliorates Peripheral Nerve Injury through Microvascular Reconstruction

Microvascular reconstruction is essential for peripheral nerve repair. S-Propargyl-cysteine (SPRC), the endogenous hydrogen sulfide (H<sub>2</sub>S) donor, has been reported to promote angiogenesis. The aim of this study is to utilize the pro-angiogenic ability of SPRC to support periphe...

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Main Authors: Haiyan Xi, Chenye Wang, Qixiu Li, Qing Ye, Yizhun Zhu, Yicheng Mao
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/12/2/294
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author Haiyan Xi
Chenye Wang
Qixiu Li
Qing Ye
Yizhun Zhu
Yicheng Mao
author_facet Haiyan Xi
Chenye Wang
Qixiu Li
Qing Ye
Yizhun Zhu
Yicheng Mao
author_sort Haiyan Xi
collection DOAJ
description Microvascular reconstruction is essential for peripheral nerve repair. S-Propargyl-cysteine (SPRC), the endogenous hydrogen sulfide (H<sub>2</sub>S) donor, has been reported to promote angiogenesis. The aim of this study is to utilize the pro-angiogenic ability of SPRC to support peripheral nerve repair and to explore the potential mechanisms. The effects and mechanisms of SPRC on angiogenesis and peripheral nerve repair were examined under hypoxic condition by establishing a sciatic nerve crushed injury model in mice and rats, and a hypoxia model in human umbilical vascular endothelial cells (HUVECs) in vitro. We found that SPRC accelerated the function recovery of the injured sciatic nerve and alleviated atrophy of the gastrocnemius muscle in mice. It facilitated the viability of Schwann cells (SCs), the outgrowth and myelination of regenerated axons, and angiogenesis in rats. It enhanced the viability, proliferation, adhesion, migration, and tube formation of HUVECs under hypoxic condition. SPRC activated sirtuin1 (SIRT1) expression by promoting the production of endogenous H<sub>2</sub>S, and SIRT1 negatively regulated Notch signaling in endothelial cells (ECs), thereby promoting angiogenesis. Collectively, our study has provided important evidence that SPRC has an effective role in peripheral nerve repair through microvascular reconstruction, which could be a potentially effective medical therapy for peripheral nerve injury.
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spelling doaj.art-d1f68597ad4a4ef9939d72ec03313db82023-11-16T18:46:08ZengMDPI AGAntioxidants2076-39212023-01-0112229410.3390/antiox12020294S-Propargyl-Cysteine Ameliorates Peripheral Nerve Injury through Microvascular ReconstructionHaiyan Xi0Chenye Wang1Qixiu Li2Qing Ye3Yizhun Zhu4Yicheng Mao5Shanghai Key Laboratory of Bioactive Small Molecules, School of Pharmacy, Fudan University, Shanghai 201203, ChinaShanghai Key Laboratory of Bioactive Small Molecules, School of Pharmacy, Fudan University, Shanghai 201203, ChinaShanghai Key Laboratory of Bioactive Small Molecules, School of Pharmacy, Fudan University, Shanghai 201203, ChinaShanghai Key Laboratory of Bioactive Small Molecules, School of Pharmacy, Fudan University, Shanghai 201203, ChinaShanghai Key Laboratory of Bioactive Small Molecules, School of Pharmacy, Fudan University, Shanghai 201203, ChinaShanghai Key Laboratory of Bioactive Small Molecules, School of Pharmacy, Fudan University, Shanghai 201203, ChinaMicrovascular reconstruction is essential for peripheral nerve repair. S-Propargyl-cysteine (SPRC), the endogenous hydrogen sulfide (H<sub>2</sub>S) donor, has been reported to promote angiogenesis. The aim of this study is to utilize the pro-angiogenic ability of SPRC to support peripheral nerve repair and to explore the potential mechanisms. The effects and mechanisms of SPRC on angiogenesis and peripheral nerve repair were examined under hypoxic condition by establishing a sciatic nerve crushed injury model in mice and rats, and a hypoxia model in human umbilical vascular endothelial cells (HUVECs) in vitro. We found that SPRC accelerated the function recovery of the injured sciatic nerve and alleviated atrophy of the gastrocnemius muscle in mice. It facilitated the viability of Schwann cells (SCs), the outgrowth and myelination of regenerated axons, and angiogenesis in rats. It enhanced the viability, proliferation, adhesion, migration, and tube formation of HUVECs under hypoxic condition. SPRC activated sirtuin1 (SIRT1) expression by promoting the production of endogenous H<sub>2</sub>S, and SIRT1 negatively regulated Notch signaling in endothelial cells (ECs), thereby promoting angiogenesis. Collectively, our study has provided important evidence that SPRC has an effective role in peripheral nerve repair through microvascular reconstruction, which could be a potentially effective medical therapy for peripheral nerve injury.https://www.mdpi.com/2076-3921/12/2/294S-propargyl-cysteinehydrogen sulfidemicrovascular reconstructionperipheral nerve injury repairsirtuin1Notch1 intracellular domain
spellingShingle Haiyan Xi
Chenye Wang
Qixiu Li
Qing Ye
Yizhun Zhu
Yicheng Mao
S-Propargyl-Cysteine Ameliorates Peripheral Nerve Injury through Microvascular Reconstruction
Antioxidants
S-propargyl-cysteine
hydrogen sulfide
microvascular reconstruction
peripheral nerve injury repair
sirtuin1
Notch1 intracellular domain
title S-Propargyl-Cysteine Ameliorates Peripheral Nerve Injury through Microvascular Reconstruction
title_full S-Propargyl-Cysteine Ameliorates Peripheral Nerve Injury through Microvascular Reconstruction
title_fullStr S-Propargyl-Cysteine Ameliorates Peripheral Nerve Injury through Microvascular Reconstruction
title_full_unstemmed S-Propargyl-Cysteine Ameliorates Peripheral Nerve Injury through Microvascular Reconstruction
title_short S-Propargyl-Cysteine Ameliorates Peripheral Nerve Injury through Microvascular Reconstruction
title_sort s propargyl cysteine ameliorates peripheral nerve injury through microvascular reconstruction
topic S-propargyl-cysteine
hydrogen sulfide
microvascular reconstruction
peripheral nerve injury repair
sirtuin1
Notch1 intracellular domain
url https://www.mdpi.com/2076-3921/12/2/294
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AT qingye spropargylcysteineamelioratesperipheralnerveinjurythroughmicrovascularreconstruction
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