Hydrogen sulfide formation in experimental model of acute pancreatitis
Hydrogen sulfide formation in experimental model of acute pancreatitis
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DOI：
10.18388/abp.2019_2900
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发表时间：
2019-01-01
影响因子：
1.7
通讯作者：
Wrobel, Maria
中科院分区：
文献类型：
--
作者：
Bronowicka-Adamska, Patrycja;Hutsch, Tomasz;Wrobel, Maria
急性胰腺炎(AP)是一种胰腺的急性或慢性炎症过程，其特征是胰腺腺泡细胞内消化酶的过早激活，导致胰腺自身消化。在哺乳动物组织中，H_2S由L-半胱氨酸在磷酸吡哆醛依赖酶(CBS、Cth)、半胱氨酸氨基转移酶(CAT)和3-巯基丙酮酸硫转移酶(MPST)的催化下内源合成。在线粒体中，硫化氢被氧化成亚硫酸盐，然后亚硫酸盐被硫代硫酸盐硫转移酶(硫代硫酸盐；TST)转化为硫代硫酸盐(一种含硫的化合物)。测定正常大鼠、急性胰腺炎大鼠和假手术组大鼠胰腺组织中CBS、Cth、MPST和TST的活性和表达。还测定了低分子硫化物的含量，如还原和氧化的谷胱甘肽、半胱氨酸、半胱氨酸和胱硫氨酸。这项研究揭示了MPST在胰腺中的H_2S代谢中的重要作用。手术(假手术组)和AP引起的应激导致H_2S生成减少，同时MPST活性和表达降低。AP胰腺中显著较高的半胱氨酸水平可能是由于MPST催化的反应中半胱氨酸消耗率降低所致，但这也可能是改变的组织中发生蛋白质分解过程的迹象。
Acute pancreatitis (AP) is a disease defined as acute or chronic inflammatory process of the pancreas characterized by premature activation of digestive enzymes within the pancreatic acinar cells and causing pancreatic auto-digestion. In mammalian tissues, H2S is synthesized endogenously from L-cysteine in regulated enzymatic pathways catalyzed by pyridoxal phosphate-dependent enzymes: cystathionine beta-synthase (CBS), gamma-cystathionase (CTH) and cysteine aminotransferase (CAT) coupled with 3-mercaptopyruvate sulfurtransferase (MPST). In the mitochondria, hydrogen sulfide is oxidized to sulfite, which is then converted to thiosulfate (a sulfane sulfur-containing compound) by thiosulfate sulfurtransferase (rhodanese; TST). Activity and expression of CBS, CTH, MPST, and TST have been determined in vivo in pancreas of the control rats, rats with acute pancreatitis and a sham group. Levels of low-molecular sulfur compounds, such as the reduced and oxidized glutathione, cysteine, cystine and cystathionine, were also determined. This study revealed a significant role of MPST in H2S metabolism in the pancreas. Stress caused by the surgery (sham group) and AP cause a decrease in H2S production associated with a decrease in MPST activity and expression. Markedly higher level of cysteine in the AP pancreas may be caused by a reduced rate of cysteine consumption in a reaction catalyzed by MPST, but it can also be a sign of proteolytic processes occurring in the changed tissue.