N-Acetyl Cysteine Restores Sirtuin-6 and Decreases HMGB1 Release Following Lipopolysaccharide-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Mice

Inflammation and neonatal hypoxia-ischemia (HI) are important etiological factors of perinatal brain injury. However, underlying mechanisms remain unclear. Sirtuins are a family of nicotinamide adenine dinucleotide (NAD)+-dependent histone deacetylases. Sirtuin-6 is thought to regulate inflammatory...

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Autores principales:	Gagandeep Singh-Mallah, Takuya Kawamura, Maryam Ardalan, Tetyana Chumak, Pernilla Svedin, Peter G. Arthur, Christopher James, Henrik Hagberg, Mats Sandberg, Carina Mallard
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	sirtuins high-mobility group box 1 protein n-acetyl cysteine hypoxia-ischemia lipopolysaccharide Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/51dc58991b0f464fb6370b70aa1027ac
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spelling	oai:doaj.org-article:51dc58991b0f464fb6370b70aa1027ac2021-11-15T04:54:29ZN-Acetyl Cysteine Restores Sirtuin-6 and Decreases HMGB1 Release Following Lipopolysaccharide-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Mice1662-510210.3389/fncel.2021.743093https://doaj.org/article/51dc58991b0f464fb6370b70aa1027ac2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fncel.2021.743093/fullhttps://doaj.org/toc/1662-5102Inflammation and neonatal hypoxia-ischemia (HI) are important etiological factors of perinatal brain injury. However, underlying mechanisms remain unclear. Sirtuins are a family of nicotinamide adenine dinucleotide (NAD)+-dependent histone deacetylases. Sirtuin-6 is thought to regulate inflammatory and oxidative pathways, such as the extracellular release of the alarmin high mobility group box-1 (HMGB1). The expression and role of sirtuin-6 in neonatal brain injury are unknown. In a well-established model of neonatal brain injury, which encompasses inflammation (lipopolysaccharide, LPS) and hypoxia-ischemia (LPS+HI), we investigated the protein expression of sirtuin-6 and HMGB1, as well as thiol oxidation. Furthermore, we assessed the effect of the antioxidant N-acetyl cysteine (NAC) on sirtuin-6 expression, nuclear to cytoplasmic translocation, and release of HMGB1 in the brain and blood thiol oxidation after LPS+HI. We demonstrate reduced expression of sirtuin-6 and increased release of HMGB1 in injured hippocampus after LPS+HI. NAC treatment restored sirtuin-6 protein levels, which was associated with reduced extracellular HMGB1 release and reduced thiol oxidation in the blood. The study suggests that early reduction in sirtuin-6 is associated with HMGB1 release, which may contribute to neonatal brain injury, and that antioxidant treatment is beneficial for the alleviation of these injurious mechanisms.Gagandeep Singh-MallahTakuya KawamuraTakuya KawamuraMaryam ArdalanTetyana ChumakPernilla SvedinPeter G. ArthurChristopher JamesHenrik HagbergHenrik HagbergMats SandbergCarina MallardFrontiers Media S.A.articlesirtuinshigh-mobility group box 1 proteinn-acetyl cysteinehypoxia-ischemialipopolysaccharideNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Cellular Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	sirtuins high-mobility group box 1 protein n-acetyl cysteine hypoxia-ischemia lipopolysaccharide Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	sirtuins high-mobility group box 1 protein n-acetyl cysteine hypoxia-ischemia lipopolysaccharide Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Gagandeep Singh-Mallah Takuya Kawamura Takuya Kawamura Maryam Ardalan Tetyana Chumak Pernilla Svedin Peter G. Arthur Christopher James Henrik Hagberg Henrik Hagberg Mats Sandberg Carina Mallard N-Acetyl Cysteine Restores Sirtuin-6 and Decreases HMGB1 Release Following Lipopolysaccharide-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Mice
description	Inflammation and neonatal hypoxia-ischemia (HI) are important etiological factors of perinatal brain injury. However, underlying mechanisms remain unclear. Sirtuins are a family of nicotinamide adenine dinucleotide (NAD)+-dependent histone deacetylases. Sirtuin-6 is thought to regulate inflammatory and oxidative pathways, such as the extracellular release of the alarmin high mobility group box-1 (HMGB1). The expression and role of sirtuin-6 in neonatal brain injury are unknown. In a well-established model of neonatal brain injury, which encompasses inflammation (lipopolysaccharide, LPS) and hypoxia-ischemia (LPS+HI), we investigated the protein expression of sirtuin-6 and HMGB1, as well as thiol oxidation. Furthermore, we assessed the effect of the antioxidant N-acetyl cysteine (NAC) on sirtuin-6 expression, nuclear to cytoplasmic translocation, and release of HMGB1 in the brain and blood thiol oxidation after LPS+HI. We demonstrate reduced expression of sirtuin-6 and increased release of HMGB1 in injured hippocampus after LPS+HI. NAC treatment restored sirtuin-6 protein levels, which was associated with reduced extracellular HMGB1 release and reduced thiol oxidation in the blood. The study suggests that early reduction in sirtuin-6 is associated with HMGB1 release, which may contribute to neonatal brain injury, and that antioxidant treatment is beneficial for the alleviation of these injurious mechanisms.
format	article
author	Gagandeep Singh-Mallah Takuya Kawamura Takuya Kawamura Maryam Ardalan Tetyana Chumak Pernilla Svedin Peter G. Arthur Christopher James Henrik Hagberg Henrik Hagberg Mats Sandberg Carina Mallard
author_facet	Gagandeep Singh-Mallah Takuya Kawamura Takuya Kawamura Maryam Ardalan Tetyana Chumak Pernilla Svedin Peter G. Arthur Christopher James Henrik Hagberg Henrik Hagberg Mats Sandberg Carina Mallard
author_sort	Gagandeep Singh-Mallah
title	N-Acetyl Cysteine Restores Sirtuin-6 and Decreases HMGB1 Release Following Lipopolysaccharide-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Mice
title_short	N-Acetyl Cysteine Restores Sirtuin-6 and Decreases HMGB1 Release Following Lipopolysaccharide-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Mice
title_full	N-Acetyl Cysteine Restores Sirtuin-6 and Decreases HMGB1 Release Following Lipopolysaccharide-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Mice
title_fullStr	N-Acetyl Cysteine Restores Sirtuin-6 and Decreases HMGB1 Release Following Lipopolysaccharide-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Mice
title_full_unstemmed	N-Acetyl Cysteine Restores Sirtuin-6 and Decreases HMGB1 Release Following Lipopolysaccharide-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Mice
title_sort	n-acetyl cysteine restores sirtuin-6 and decreases hmgb1 release following lipopolysaccharide-sensitized hypoxic-ischemic brain injury in neonatal mice
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/51dc58991b0f464fb6370b70aa1027ac
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N-Acetyl Cysteine Restores Sirtuin-6 and Decreases HMGB1 Release Following Lipopolysaccharide-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Mice

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