Transsulfuration Pathway Defects and Increased Glutathione Degradation in Severe Acute Pancreatitis

Rahman, Sunniyat; Srinivasan, Asha; Nicolaou, Anna

doi:10.1007/s10620-008-0382-z

Cited by 8 publications

(5 citation statements)

References 53 publications

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“…Hence, methionine metabolism through the trans-sulfuration pathway and the trans-methylation system decisively contributes to the maintenance of redox homeostasis in cells [6]. Increased levels of homocysteine, a sign of dysregulation of the trans-sulfuration pathway, have been detected in plasma of patients with a variety of gastrointestinal disorders including inflammatory bowel disease [7,8], colorectal cancer [9] as well as acute pancreatitis [10].…”

Section: Introductionmentioning

confidence: 99%

Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine β-synthase

et al. 2020

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Acute pancreatitis is an inflammatory process of the pancreatic gland that may lead to dysregulation of the trans-sulfuration pathway. The aims of this work were firstly to study the methionine cycle as well as the trans-sulfuration pathway using metabolomic and proteomic approaches identifying the causes of this dysregulation in an experimental model of acute pancreatitis; and secondly to reveal the effects of S-adenosylmethionine administration on these pathways. Acute pancreatitis was induced by cerulein in mice, and a group of animals received S-adenosylmethionine treatment. Cerulein-induced acute pancreatitis rapidly caused marked depletion of methionine, S-adenosylmethionine, 5′-methylthioadenosine, cystathionine, cysteine, and glutathione levels in pancreas, but S-adenosylhomocysteine and homocysteine remained unchanged. Protein steady-state levels of S-adenosylhomocysteine-hydrolase and cystathionine gamma-lyase diminished but methylthioadenosine phosphorylase levels increased in pancreas with acute pancreatitis. Although cystathionine β-synthase protein levels did not change with acute pancreatitis, Nos2 mRNA and protein levels were markedly up-regulated and caused tyrosine nitration of cystathionine β-synthase in pancreas. S-adenosylmethionine administration enhanced Nos2 mRNA expression and cystathionine β-synthase nitration and triggered homocysteine accumulation in acute pancreatitis. Furthermore, S-adenosylmethionine administration promoted enrichment of the euchromatin marker H3K4me3 in the promoters of Tnf-α, Il-6, and Nos2 and enhanced the mRNA up-regulation of these genes. Accordingly, S-adenosylmethionine administration increased inflammatory infiltrate and edema in pancreas with acute pancreatitis. In conclusion, tyrosine-nitration of cystathionine β-synthase blockades the trans-sulfuration pathway in acute pancreatitis promoting homocysteine accumulation upon S-adenosylmethionine treatment.

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Section: Introductionmentioning

confidence: 99%

Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine β-synthase

et al. 2020

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“…Transsulfuration impairment is also associated with other disorders such as autism [4–8], cirrhosis [9–13], coronary artery disease [14–18], goiter [19], impaired coagulation [20–22], immune function [23], neurodegenerative disease [24–26], and pancreatitis [27]. This variety of afflictions highlights the importance of transsulfuration to human health.…”

Section: Introductionmentioning

confidence: 99%

“…Despite the widespread nature of tissues involved in these disorders, our knowledge of transsulfuration is confined to the liver and a small number of other tissues. These include the brain [28], certain lymphoid cells [29], and the pancreas [27, 30]. …”

Section: Introductionmentioning

confidence: 99%

Transsulfuration Is a Significant Source of Sulfur for Glutathione Production in Human Mammary Epithelial Cells

et al. 2013

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The transsulfuration pathway, through which homocysteine from the methionine cycle provides sulfur for cystathionine formation, which may subsequently be used for glutathione synthesis, has not heretofore been identified as active in mammary cells. Primary human mammary epithelial cells (HMEC’s) were labeled with 35S-methionine for 24 hours following pretreatment with a vehicle control, the cysteine biosynthesis inhibitor propargylglycine or the gamma-glutamylcysteine synthesis inhibitor buthionine sulfoximine. Cell lysates were prepared and reacted with glutathione-S-transferase and the fluorescent labeling compound monochlorobimane to form a fluorescent glutathione-bimane conjugate. Comparison of fluorographic and autoradiographic images indicated that glutathione had incorporated 35S-methionine demonstrating that functional transsulfuration occurs in mammary cells. Pathway inhibitors reduced incorporation by roughly 80%. Measurement of glutathione production in HMEC’s treated with and without hydrogen peroxide and/or pathway inhibitors indicates that the transsulfuration pathway plays a significant role in providing cysteine for glutathione production both normally and under conditions of oxidant stress.

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“…Abu-Zidan et al ( 42 ) demonstrated that OS markers are positively correlated with the severity of pancreatitis. In addition, AP is characterized by pancreatic glutathione depletion ( 50 , 51 ). Rahman et al ( 51 ) reported that decreased concentration of glutathione is associated with increased level of its metabolite cysteinyl glycine, which might induce severe AP.…”

Section: Antioxidants and Oxidative Stressmentioning

confidence: 99%

Role of antioxidants and oxidative stress in the evolution of acute pancreatitis (Review)

et al. 2022

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Acute pancreatitis (AP) is a severe disease with a high prevalence and 3 to 15% mortality worldwide, which can represent an important challenge for the physician. Oxidative stress and antioxidants are involved in AP progression. The mechanisms responsible for the onset and progression of AP are still poorly understood. Previous studies have highlighted the important contribution of antioxidants and oxidative stress in AP. The existence of a relationship between oxidative stress and antioxidants in AP is unquestionable, although a more accurate understanding of the mechanistic pathways involved is required to create a solid basis for potential prevention or treatment strategies. Further investigation is needed to clarify the role of antioxidant status and the severity of AP and to determine the association between oxidative stress and pancreatic enzyme activities. Antioxidant therapy may represent an interesting option for the management of patients with AP, although additional information about the effectiveness of this potential treatment is required. Contents 1. Introduction 2. Methods 3. Antioxidants and oxidative stress 4. Conclusions

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Transsulfuration Pathway Defects and Increased Glutathione Degradation in Severe Acute Pancreatitis

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Cited by 8 publications

References 53 publications

Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine β-synthase

Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine β-synthase

Transsulfuration Is a Significant Source of Sulfur for Glutathione Production in Human Mammary Epithelial Cells

Role of antioxidants and oxidative stress in the evolution of acute pancreatitis (Review)

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