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急性胰腺炎实验模型中硫化氢的形成

Hydrogen sulfide formation in experimental model of acute pancreatitis.

作者信息

Bronowicka-Adamska Patrycja, Hutsch Tomasz, Gawryś-Kopczyńska Marta, Maksymiuk Klaudia, Wróbel Maria

机构信息

Chair of Medical Biochemistry, Jagiellonian University, Collegium Modicum, Kraków, Poland.

Department of Physiology and Experimental Pathophysiology, Medical University of Warsaw, Warsaw, Poland.

出版信息

Acta Biochim Pol. 2019 Dec 27;66(4):611-618. doi: 10.18388/abp.2019_2900.

DOI:10.18388/abp.2019_2900
PMID:31893496
Abstract

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 (sulfane sulfur-containing compound) by thiosulfate sulfurtransferase (rhodanese; TST). The activity and the expression of CBS, CTH, MPST, and TST have been determined in vivo in pancreas of control rats, rats with acute pancreatitis and sham group. Levels of low-molecular sulfur compounds such as reduced and oxidized glutathione, cysteine, cystine and cystathionine were also determined. The study showed the significant role of MPST in H2S metabolism in pancreas. Stress caused by the surgery (sham group) and AP cause a decrease in H2S production associated with a decrease of MPST activity and expression. Markedly higher level of cysteine in the AP pancreas may be caused by a reduced rate of cysteine consumption in reaction catalyzed by MPST but it can also be a sign of the processes of proteolysis occurring in the changed tissue.

摘要

急性胰腺炎(AP)是一种被定义为胰腺的急性或慢性炎症过程的疾病,其特征是胰腺腺泡细胞内消化酶过早激活并导致胰腺自身消化。在哺乳动物组织中,硫化氢(H2S)由L-半胱氨酸通过磷酸吡哆醛依赖性酶催化的调节性酶促途径内源性合成:胱硫醚β-合酶(CBS)、γ-胱硫醚酶(CTH)和半胱氨酸转氨酶(CAT)与3-巯基丙酮酸硫转移酶(MPST)偶联。在线粒体中,硫化氢被氧化为亚硫酸盐,然后通过硫代硫酸盐硫转移酶(硫氰酸酶;TST)转化为硫代硫酸盐(含硫烷硫的化合物)。已在对照大鼠、急性胰腺炎大鼠和假手术组大鼠的胰腺中体内测定了CBS、CTH、MPST和TST的活性及表达。还测定了低分子硫化合物如还原型和氧化型谷胱甘肽、半胱氨酸、胱氨酸和胱硫醚的水平。该研究表明MPST在胰腺H2S代谢中起重要作用。手术(假手术组)和AP引起的应激导致H2S产生减少,这与MPST活性和表达降低有关。AP胰腺中半胱氨酸水平明显升高可能是由于MPST催化的反应中半胱氨酸消耗速率降低所致,但也可能是病变组织中发生蛋白水解过程的一个迹象。

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