Acetylcysteine modulates sphingolipid levels by inhibiting neutral sphingomyelinase during aging in rat tissues

IF 0.4 4区 医学 Q4 PHARMACOLOGY & PHARMACY
L. Hassouneh, Salameh Aldajah, M. Najdawi, Z. Abudayeh, Qais Abualassal, Amajad aburmelah, Alaa Sirhan
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引用次数: 0

Abstract

Old-age-associated pathologies usually coincide with altered sphingolipid metabolism. Changes in the level of sphingomyelin (SM) and ceramide are largely determined by the activation of neutral sphingomyelinase (nSMase) during aging. nSMase is a key enzyme in sphingolipid turnover; it generates ceramide through the hydrolysis of SM. While N—acetylcysteine (NAC) is a powerful antioxidant which has anti-inflammatory properties and it is the precursor of glutathione (GSH). The aim of this study is to determine the impact of NAC on nSMase activity in the age-dependent changes of sphingolipid (SM and ceramide) levels and GSH content in blood serum, gastrocnemius muscle and kidney tissue of 24-month-old rats. It was found that the effect of NAC on the tissue of 24-month-old rats increased SM content; GSH content and decreased the ceramide content. The gastrocnemius muscle and kidney were the most sensitive to the effects of NAC. The results show that GSH inhibit the activity of nSMase. These results emphasize that nSMase. plays a key role in age-associated ceramide accumulation in rat tissues during aging. Furthermore, it was indicated that NAC is an effective modulator of nSMase and has pleiotropic effects that may alter sphingolipid metabolism. The nSMase inhibition enhances the benefits of NAC treatment.
在大鼠组织衰老过程中,乙酰半胱氨酸通过抑制中性鞘磷脂酶调节鞘脂水平
老年相关病理通常与鞘脂代谢改变相一致。鞘磷脂(SM)和神经酰胺水平的变化在很大程度上是由中性鞘磷脂酶(nSMase)在衰老过程中的激活所决定的。nSMase是鞘脂转换的关键酶;它通过SM水解产生神经酰胺。而n -乙酰半胱氨酸(NAC)是一种强大的抗氧化剂,具有抗炎特性,它是谷胱甘肽(GSH)的前体。本研究旨在确定NAC对nSMase活性在24月龄大鼠血清、腓肠肌和肾脏组织中鞘脂(SM和神经酰胺)水平和GSH含量的年龄依赖性变化中的影响。结果表明,NAC对24月龄大鼠组织的影响使SM含量增加;GSH含量降低,神经酰胺含量降低。腓肠肌和肾脏对NAC的影响最为敏感。结果表明,谷胱甘肽能抑制nSMase的活性。这些结果强调了nSMase。在衰老过程中,在大鼠组织中与年龄相关的神经酰胺积累中起关键作用。此外,NAC是一种有效的nSMase调节剂,具有多效性,可能改变鞘脂代谢。nSMase的抑制增强了NAC治疗的益处。
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来源期刊
CiteScore
0.80
自引率
0.00%
发文量
74
审稿时长
6-12 weeks
期刊介绍: The international journal of the Polish Pharmaceutical Society is published in 6 issues a year. The journal offers Open Access publication of original research papers, short communications and reviews written in English, in all areas of pharmaceutical sciences. The following areas of pharmaceutical sciences are covered: Analysis, Biopharmacy, Drug Biochemistry, Drug Synthesis, Natural Drugs, Pharmaceutical Technology, Pharmacology and General. A bimonthly appearing in English since 1994, which continues “Acta Poloniae Pharmaceutica”, whose first issue appeared in December 1937. The war halted the activity of the journal’s creators. Issuance of “Acta Poloniae Pharmaceutica” was resumed in 1947. From 1947 the journal appeared irregularly, initially as a quarterly, then a bimonthly. In the years 1963 – 1973 alongside the Polish version appeared the English edition of the journal. Starting from 1974 only works in English are published in the journal. Since 1995 the journal has been appearing very regularly in two-month intervals (six books a year). The journal publishes original works from all fields of pharmacy, summaries of postdoctoral dissertations and laboratory notes.
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