High-concentration homocysteine inhibits mitochondrial respiration function and production of reactive oxygen species in neuron cells

Background: Chronic pancreatitis (CP) is a long-term risk factor for pancreatic ductal adenocarcinoma (PDAC), and both diseases share a common etiology. The activation of Pancreatic stellate cells (PaSCs) caused by inflammation of the chronic pancreas plays a pivotal role in the pathology of pancreatic fibrosis and the malignant phenotype of PDAC. However, the central role of activated PaSCs in acinar-to-ductal metaplasia (ADM) remains unknown. Objective: In the present study, we investigated the link between pancreatic fibrosis and ADM and the possible underlying mechanism. Methods: A caerulein-treated mouse CP model was established, and Masson trichrome histochemical stain and transmission electron microscope (TEM) were used to observe stromal fibrosis and cell ultrastructure, respectively. The expression of amylase and cytokeratin 19 (CK19), mitochondria respiration, and reactive oxygen species (ROS) were detected in vitro in the co-culture model of primary pancreatic acinar cells and PaSCs. Results: The activation of PaSCs and pancreatic fibrosis were accompanied by ADM in pancreatic parenchyma in caerulein-treated mice, which was verified by the co-cultivation experiment in vitro. Furthermore, we showed that activated PaSCs promote ADM by disrupting mitochondrial respiration and releasing ROS. The expression of inflammation-and ADM-related genes, including S100A8, S100A9, and CK19, was observed to be up-regulated in pancreatic acinar cells in the presence of activated PaSCs. The expression of S100A9 and CK19 proteins was also up-regulated in acinar cells co-cultured with activated PaSCs. Conclusion: The manipulation of mitochondrial respiration and ROS release is a promising preventive and/or therapeutic strategy for PDAC, and S100A9 is expected to be a therapeutic target to block the ADM process induced by the activation of PaSCs.

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Enhanced reactive oxygen species via in situ producing H2O2 and synchronous catalytic conversion at stable modified copper foam cathode for efficient high-concentration organic wastewater treatment and simultaneous electricity generation

Chemosphere ◽

10.1016/j.chemosphere.2021.132911 ◽

2021 ◽

pp. 132911

Author(s):

Yufeng Sun ◽

Leyang Shen ◽

Qin Qin ◽

Liwen Jiang ◽

Yaqian Su ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Wastewater Treatment ◽

Electricity Generation ◽

Reactive Oxygen ◽

Catalytic Conversion ◽

Oxygen Species ◽

High Concentration ◽

Copper Foam ◽

Organic Wastewater

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Mitochondria, oxidative stress and aging

Orvosi Hetilap ◽

10.1556/oh.2014.29852 ◽

2014 ◽

Vol 155 (12) ◽

pp. 447-452

Author(s):

András Szarka ◽

Gábor Bánhegyi ◽

Balázs Sümegi

Keyword(s):

Reactive Oxygen Species ◽

Mitochondrial Dna ◽

Mitochondrial Respiration ◽

Accelerated Aging ◽

Reactive Oxygen ◽

Oxygen Species ◽

Vicious Cycle ◽

Free Radical Theory ◽

Radical Theory ◽

Theory Of Aging

The free radical theory of aging was defined in the 1950s. On the base of this theory, the reactive oxygen species formed in the metabolic pathways can play pivotal role in ageing. The theory was modified by defining the mitochondrial respiration as the major cellular source of reactive oxygen species and got the new name mitochondrial theory of aging. Later on the existence of a “vicious cycle” was proposed, in which the reactive oxygen species formed in the mitochondrial respiration impair the mitochondrial DNA and its functions. The formation of reactive oxygen species are elevated due to mitochondrial dysfunction. The formation of mitochondrial DNA mutations can be accelerated by this “vicious cycle”, which can lead to accelerated aging. The exonuclease activity of DNA polymerase γ, the polymerase responsible for the replication of mitochondrial DNA was impaired in mtDNA mutator mouse recently. The rate of somatic mutations in mitochondrial DNA was elevated and an aging phenotype could have been observed in these mice. Surprisingly, no oxidative impairment neither elevated reactive oxygen species formation could have been observed in the mtDNA mutator mice, which may question the existence of the “vicious cycle”. Orv. Hetil., 2014, 155(12), 447–452.

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