GPx1 deficiency confers increased susceptibility to ferroptosis in macrophages from individuals with active Crohn’s disease DOI
James A. Sousa, Blanca E. Callejas, Arthur Wang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 5, 2024

Abstract Intestinal cell death is a defining feature of Crohn’s disease (CD), major form inflammatory bowel disease. The focus on this aspect enteric inflammation has mainly been epithelial cells, while other types such as stromal and myeloid cells have received less attention. Hypothesising that decreased macrophage viability in an oxidative environment could be contributing factor to the pathophysiology CD, we found monocyte-derived macrophages from individuals with active CD (but not those clinical remission) increased sensitivity induced by H2O2. Molecular biology pharmacological studies ruled out apoptosis necroptosis, lipid peroxidation surface expression transferrin receptor implicated ferroptosis mechanism H2O2-induced death: was supported suppression H2O2-cytotoxicity liproxstatin-1, inhibitor ferroptosis. Selenoproteins are important antioxidants, selenium deficiency can CD. Despite normal dietary intake selenium, intestinal had protein and/or mRNA selenoprotein, glutathione peroxidase (GPx)-1. Knockdown GPx1 healthy volunteers resulted reminiscent observed In summary, susceptibility death, may facilitated, at least part, reduced antioxidant GPx1. We suggest monocytes recruited gut renders these vulnerable reactive oxygen species-evoked unravelling participation pathway reveal novel therapeutic approaches chronic condition.

Language: Английский

Energy metabolism and the intestinal barrier: implications for understanding and managing intestinal diseases DOI Creative Commons
Daiwen Chen,

Caifei Shen,

Xiaorui Zeng

et al.

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 31, 2025

The interplay between energy metabolism and the gut barrier is crucial for maintaining intestinal physiological homeostasis. Energy perform distinct yet complementary roles that uphold ecological equilibrium. Disruptions in can compromise integrity of barrier; example, inactivation AMPK pathway may lead to reduced expression proteins associated with tight junctions. Conversely, impairment result metabolic dysregulation, such as alterations microbiota impede production short-chain fatty acids (SCFAs), which are essential substrates metabolism. This disruption affect modify gut's hypoxic environment. Imbalances these systems have been onset various diseases. Research indicates dietary interventions, a low FODMAP diet, enhance colonization probiotics improve fermentation SCFAs. Pharmacological strategies elevate SCFA levels activate rectify abnormalities review provides comprehensive summary recent advancements elucidating interactions barrier.

Language: Английский

Citations

0
Gene expression profile in ulcerative colitis patients: FOXO4, ALDOB, SLC26A3, SOD2 genes as potential biomarkers DOI
Yakup Ülger, Anıl Delik

Genes & Genomics, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Language: Английский

Citations

0
GPx1 deficiency confers increased susceptibility to ferroptosis in macrophages from individuals with active Crohn’s disease DOI Creative Commons
James A. Sousa, Blanca E. Callejas, Arthur Wang

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(12)

Published: Dec. 18, 2024

Abstract Intestinal cell death is a defining feature of Crohn’s disease (CD), major form inflammatory bowel disease. The focus on this aspect enteric inflammation has mainly been epithelial cells, while other types such as stromal and myeloid cells have received less attention. Hypothesising that decreased macrophage viability in an oxidative environment could be contributing factor to the pathophysiology CD, we found monocyte-derived macrophages from individuals with active CD (but not those clinical remission) increased sensitivity induced by H 2 O . Molecular biology pharmacological studies ruled out apoptosis necroptosis, lipid peroxidation surface expression transferrin receptor implicated ferroptosis mechanism -induced death: was supported suppression -cytotoxicity liproxstatin-1, inhibitor ferroptosis. Selenoproteins are important antioxidants, selenium deficiency can CD. Despite normal dietary intake selenium, intestinal had protein and/or mRNA selenoprotein, glutathione peroxidase (GPx)-1. Knockdown GPx1 healthy volunteers resulted reminiscent observed In summary, susceptibility death, may facilitated, at least part, reduced antioxidant GPx1. We suggest monocytes recruited gut renders these vulnerable reactive oxygen species-evoked unraveling participation pathway reveal novel therapeutic approaches chronic condition.

Language: Английский

Citations

2
Underneath the Gut–Brain Axis in IBD—Evidence of the Non-Obvious DOI Open Access
Lidiya V. Boldyreva, A. A. Evtushenko, Maria Lvova

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12125 - 12125

Published: Nov. 12, 2024

The gut–brain axis (GBA) plays a pivotal role in human health and wellness by orchestrating complex bidirectional regulation influencing numerous critical processes within the body. Over past decade, research has increasingly focused on GBA context of inflammatory bowel disease (IBD). Beyond its well-documented effects GBA–enteric nervous system vagus nerve dysregulation, gut microbiota misbalance—IBD also leads to impairments metabolic cellular functions: mitochondrial dysfunction, cationic transport, cytoskeleton dysregulation. These systemic are currently underexplored relation GBA; however, they crucial for cells’ functioning. This review summarizes studies particular mechanisms IBD. Understanding involvement these may help find new therapeutic targets develop approaches improve quality life IBD patients.

Language: Английский

Citations

1
GPx1 deficiency confers increased susceptibility to ferroptosis in macrophages from individuals with active Crohn’s disease DOI
James A. Sousa, Blanca E. Callejas, Arthur Wang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 5, 2024

Abstract Intestinal cell death is a defining feature of Crohn’s disease (CD), major form inflammatory bowel disease. The focus on this aspect enteric inflammation has mainly been epithelial cells, while other types such as stromal and myeloid cells have received less attention. Hypothesising that decreased macrophage viability in an oxidative environment could be contributing factor to the pathophysiology CD, we found monocyte-derived macrophages from individuals with active CD (but not those clinical remission) increased sensitivity induced by H2O2. Molecular biology pharmacological studies ruled out apoptosis necroptosis, lipid peroxidation surface expression transferrin receptor implicated ferroptosis mechanism H2O2-induced death: was supported suppression H2O2-cytotoxicity liproxstatin-1, inhibitor ferroptosis. Selenoproteins are important antioxidants, selenium deficiency can CD. Despite normal dietary intake selenium, intestinal had protein and/or mRNA selenoprotein, glutathione peroxidase (GPx)-1. Knockdown GPx1 healthy volunteers resulted reminiscent observed In summary, susceptibility death, may facilitated, at least part, reduced antioxidant GPx1. We suggest monocytes recruited gut renders these vulnerable reactive oxygen species-evoked unravelling participation pathway reveal novel therapeutic approaches chronic condition.

Language: Английский

Citations

0