Inhibition of endoplasmic reticulum stress by 4-phenylbutyric acid prevents vital organ injury in rat acute pancreatitis

Hong, Yupu; Deng, Wen-feng; W, Guo; Shi, Qiao; Zhao, Liang; You, Yun-dong; Mei, Fangchao; Zhou, Yu; Wang, Chenyang; Chen, Chen; Yu, Jie-Ping; Wang, Weixing

doi:10.1152/ajpgi.00102.2018

Cited by 26 publications

(18 citation statements)

References 36 publications

(37 reference statements)

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“…Xu et al [25] demonstrated that SPB can suppress the expression of TNF-α, IL-1β, and IL-6, and can reduce neutrophil infiltration in mice liver. In the present study, as a kind of nutritional compound, SPB had no obvious inflammatory responses in MAC-T cells; however, pretreatment with SPB significantly decreased the expression of three pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in LTA-stimulated MAC-T, which is in agreement with previous studies [23,24,25].…”

Section: Discussionsupporting

confidence: 93%

“…Cytokines, an essential component of inflammatory mediators, play a crucial role in the process of inflammation. Hong et al [23] found that SPB decreased the levels of pro-inflammatory TNF-α and IL-1β in serum of rat with acute pancreatitis. Zeng et al [24] showed that SPB reduced the release of the pro-inflammatory mediators, IL-1β, TNF-α and IL-6, and significantly inhibited lipopolysaccharide (LPS)-activated endoplasmic reticulum (ER) stress in A549 cells.…”

Section: Discussionmentioning

confidence: 99%

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Sodium Phenylbutyrate Ameliorates Inflammatory Response Induced by Staphylococcus aureus Lipoteichoic Acid via Suppressing TLR2/NF-κB/NLRP3 Pathways in MAC-T Cells

et al. 2018

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This study aimed to investigate the anti-inflammatory properties of sodium phenylbutyrate (SPB) against Staphylococcus aureus (S. aureus) lipoteichoic acid (LTA)-stimulated bovine mammary alveolar (MAC-T) cells. Quantitative PCR was performed to examine the effect of SPB on inflammatory cytokines and host defense peptide (HDP) gene expression. Western blot wanalysis was used to detect the effect of SPB on the TLR2/NF-κB/NLRP3 signaling pathway. The results showed that SPB significantly suppressed the expression of TNF-α, IL-1β, IL-6; meanwhile, the markedly decreased expression of LTA-stimulated TLR2, NLRP3, ASC, caspase-1, and IL-1β, and the inhibited IkBα and p65 phosphorylation were also observed. However, increased TAP and Bac5 expression in LTA-stimulated MAC-T cells was further detected. In summary, these results suggest that SPB ameliorates the inflammatory response induced by S. aureus LTA via suppressing the TLR2/NF-κB/NLRP3 signaling pathway, which indicates that SPB may be a potential agent for the treatment of bovine mastitis.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Sodium Phenylbutyrate Ameliorates Inflammatory Response Induced by Staphylococcus aureus Lipoteichoic Acid via Suppressing TLR2/NF-κB/NLRP3 Pathways in MAC-T Cells

et al. 2018

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“…ER transmembrane proteins sense the folding state of proteins inside the ER lumen and convey the information to the mitochondria and the cytosol. 4-PBA, an ERS inhibitor, acts as a chemical chaperone assisting protein folding in the ER as well as in the cytosol and the mitochondria [47]. In our results, inhibition of ROS with antioxidant NAC and mitigation of ERS with ERS inhibitor 4-PBA obviously suppressed ADE-induced apoptosis and the expression of ERS-related proteins.…”

Section: Discussionsupporting

confidence: 56%

Acetaldehyde Induces Neurotoxicity In Vitro via Oxidative Stress- and Ca²⁺ Imbalance-Mediated Endoplasmic Reticulum Stress

Cui

Liu

Chang

et al. 2019

Oxidative Medicine and Cellular Longevity

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Excessive drinking can damage brain tissue and cause cognitive dysfunction. Studies have found that the early stage of neurodegenerative disease is closely related to heavy drinking. Acetaldehyde (ADE) is the main toxic metabolite of alcohol. However, the exact mechanisms of ADE-induced neurotoxicity are not fully clear. In this article, we studied the cytotoxic effect of ADE in HT22 cells and primary cultured cortical neuronal cells. We found that ADE exhibited cytotoxicities against HT22 cells and primary cultured cortical neuronal cells in dose-dependent manners. Furthermore, ADE induced apoptosis of HT22 cells by upregulating the expression of caspase family proapoptotic proteins. Moreover, ADE treatment could significantly increase the intracellular Ca2+ and reactive oxygen species (ROS) levels and activate endoplasmic reticulum stress (ERS) in HT22 cells. ADE upregulated ERS-related CHOP expression dose-dependently in primary cultured cortical neuronal cells. In addition, inhibition of ROS with antioxidant N-acetyl-L-cysteine (NAC) reduced the accumulation of ROS and reversed ADE-induced increase of ERS-related protein and apoptosis-related protein levels. Mitigation of ERS with ERS inhibitor 4-PBA obviously suppressed ADE-induced apoptosis and the expression of ERS-related proteins. Therefore, ADE induces neurotoxicity of HT22 cells via oxidative stress- and Ca2+ imbalance-mediated ERS.

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“…Pancreas Immunostaining. Sections for immunostaining were processed with previous methods [18]. After deparaffinization, hydration, antigen retrieval, and serum blocking, the sections were incubated overnight at 4°C with primary antibodies: MPO (1 : 400, Servicebio, Wuhan, China, Cat no.…”

Section: Pancreatic Injury Assessmentmentioning

confidence: 99%

High-Fat Diet Aggravates Acute Pancreatitis via TLR4-Mediated Necroptosis and Inflammation in Rats

Hong

et al. 2020

Oxidative Medicine and Cellular Longevity

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High-fat diet (HFD) often increases oxidative stress and enhances inflammatory status in the body. Toll-like receptor 4 (TLR4) is widely expressed in the pancreatic tissues and plays an important role in pancreatitis. This study is aimed at investigating the effect of HFD on acute pancreatitis (AP) and the role of TLR4-mediated necroptosis and inflammation in this disease. Weight-matched rats were allocated for an 8-week feeding on the standard chow diet (SCD) or HFD, and then, the AP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. Rats were sacrificed at an indicated time point after modeling. Additionally, inhibition of TLR4 signaling by TAK-242 in HFD rats with AP was conducted in vivo. The results showed that the levels of serum free fatty acid (FFA) in HFD rats were higher than those in SCD rats. Moreover, HFD rats were more vulnerable to AP injury than SCD rats, as indicated by more serious pathological damage and much higher pancreatic malondialdehyde (MDA) and lipid peroxidation (LPO) levels as well as lower pancreatic superoxide dismutase (SOD) activities and reduced glutathione (GSH) contents and more intense infiltration of MPO-positive neutrophils and CD68-positive macrophages. In addition, HFD markedly increased the expressions of TLR4 and necroptosis marker (RIP3) and aggravated the activation of NF-κB p65 and the expression of TNF-α in the pancreas of AP rats at indicated time points. However, TLR4 inhibition significantly attenuated the structural and functional damage of the pancreas induced by AP in HFD rats, as indicated by improvement of the above indexes. Taken together, these findings suggest that HFD exacerbated the extent and severity of AP via oxidative stress, inflammatory response, and necroptosis. Inhibition of TLR4 signaling by TAK-242 alleviated oxidative stress and decreased inflammatory reaction and necroptosis, exerting a protective effect during AP in HFD rats.

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Inhibition of endoplasmic reticulum stress by 4-phenylbutyric acid prevents vital organ injury in rat acute pancreatitis

Cited by 26 publications

References 36 publications

Sodium Phenylbutyrate Ameliorates Inflammatory Response Induced by Staphylococcus aureus Lipoteichoic Acid via Suppressing TLR2/NF-κB/NLRP3 Pathways in MAC-T Cells

Sodium Phenylbutyrate Ameliorates Inflammatory Response Induced by Staphylococcus aureus Lipoteichoic Acid via Suppressing TLR2/NF-κB/NLRP3 Pathways in MAC-T Cells

Acetaldehyde Induces Neurotoxicity In Vitro via Oxidative Stress- and Ca²⁺ Imbalance-Mediated Endoplasmic Reticulum Stress

High-Fat Diet Aggravates Acute Pancreatitis via TLR4-Mediated Necroptosis and Inflammation in Rats

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Inhibition of endoplasmic reticulum stress by 4-phenylbutyric acid prevents vital organ injury in rat acute pancreatitis

Cited by 26 publications

References 36 publications

Sodium Phenylbutyrate Ameliorates Inflammatory Response Induced by Staphylococcus aureus Lipoteichoic Acid via Suppressing TLR2/NF-κB/NLRP3 Pathways in MAC-T Cells

Sodium Phenylbutyrate Ameliorates Inflammatory Response Induced by Staphylococcus aureus Lipoteichoic Acid via Suppressing TLR2/NF-κB/NLRP3 Pathways in MAC-T Cells

Acetaldehyde Induces Neurotoxicity In Vitro via Oxidative Stress- and Ca2+ Imbalance-Mediated Endoplasmic Reticulum Stress

High-Fat Diet Aggravates Acute Pancreatitis via TLR4-Mediated Necroptosis and Inflammation in Rats

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Acetaldehyde Induces Neurotoxicity In Vitro via Oxidative Stress- and Ca²⁺ Imbalance-Mediated Endoplasmic Reticulum Stress