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高血压和衰老影响大鼠肝脏硫代谢。

Hypertension and Aging Affect Liver Sulfur Metabolism in Rats.

机构信息

Jagiellonian University Medical College, Faculty of Medicine, Chair of Medical Biochemistry, 7 Kopernika St., 31-034 Kraków, Poland.

Laboratory of the Centre for Preclinical Research, Department of Physiology and Experimental Pathophysiology, Medical University of Warsaw, 1B Banacha St., 02-097 Warsaw, Poland.

出版信息

Cells. 2021 May 18;10(5):1238. doi: 10.3390/cells10051238.

Abstract

Hypertension and age are key risk factors for cardiovascular morbidity and mortality. Hydrogen sulfide (HS), a gaseous transmitter, contributes significantly to regulating arterial blood pressure and aging processes. This study evaluated the effects of hypertension and aging on the hepatic metabolism of sulfur-containing compounds, the activity of the enzymes involved in sulfur homeostasis, and the liver's ability to generate HS. Livers isolated from 16- and 60-week-old normotensive Wistar Kyoto rats (WKY) and Spontaneously Hypertensive Rats (SHR) were used to evaluate gene expression using RT-PCR, and the activity of enzymes participating in HS metabolism, including thiosulfate sulfurtransferase (rhodanese; TST), cystathionine gamma-lyase (CTH), and 3-mercaptopyruvate sulfurtransferase (MPST). The levels of cysteine, cystine, reduced and oxidized glutathione were measured using RP-HPLC. SHR livers from both age groups showed a higher capacity to generate HS than livers from WKY. The gene expression and activity of enzymes involved in sulfur metabolism differed between WKY and SHR, and between the age groups. For example, 16-week-old SHR had significantly higher activity of TST than 16-week-old WKY. Furthermore, differences between younger and older WKY rats in the expression and/or activity of TST and MPST were present. In conclusion, our study shows that arterial hypertension and aging affect hepatic sulfur metabolism and HS production in rats. These findings pave the way for interventional studies evaluating a potential causal relation between liver sulfur metabolism, hypertension and aging.

摘要

高血压和年龄是心血管发病率和死亡率的主要危险因素。硫化氢(HS)作为一种气态递质,对调节动脉血压和衰老过程有重要贡献。本研究评估了高血压和衰老对含硫化合物肝脏代谢、参与硫稳态的酶活性以及肝脏产生 HS 能力的影响。使用来自 16 周和 60 周龄正常血压 Wistar Kyoto 大鼠(WKY)和自发性高血压大鼠(SHR)的肝脏,通过 RT-PCR 评估基因表达,并评估参与 HS 代谢的酶的活性,包括硫代硫酸盐硫转移酶(rhodanese;TST)、胱硫醚γ-裂解酶(CTH)和 3-巯基丙酮酸硫转移酶(MPST)。使用反相高效液相色谱法(RP-HPLC)测量半胱氨酸、胱氨酸、还原型和氧化型谷胱甘肽的水平。来自两个年龄组的 SHR 肝脏生成 HS 的能力高于 WKY 肝脏。WKY 和 SHR 之间以及两个年龄组之间,参与硫代谢的基因表达和酶活性存在差异。例如,16 周龄 SHR 的 TST 活性明显高于 16 周龄 WKY。此外,年轻和年长 WKY 大鼠之间 TST 和 MPST 的表达和/或活性存在差异。总之,我们的研究表明,动脉高血压和衰老影响大鼠肝脏的硫代谢和 HS 生成。这些发现为评估肝脏硫代谢、高血压和衰老之间潜在因果关系的干预研究铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4634/8157544/8aadba9eb3cd/cells-10-01238-g001.jpg

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