scholarly journals Epigenetic changes in inflammatory genes and the protective effect of cooked rhubarb on pancreatic tissue of rats with chronic alcohol exposure

2022 ◽  
Vol 146 ◽  
pp. 112587
Author(s):  
Xianlin Zhao ◽  
Shifeng Zhu ◽  
Juan Li ◽  
Dan Long ◽  
Meihua Wan ◽  
...  
Author(s):  
Lin Ye ◽  
Shuhao Li ◽  
Xiaochen Liu ◽  
Dingang Zhang ◽  
Liliang Li ◽  
...  

Abstract Aims Alcohol abuse induces multiple neuropathology and causes global burden to human health. Prefrontal cortex (PFC) is one of the most susceptible regions to alcohol-induced neuropathology. However, precise mechanisms underlying these effects on PFC remain to be elucidated. Herein, we investigated whether RIP1/RIP3/MLKL-mediated necroptosis was involved in the alcohol-induced PFC injury, and explored the effect that cannabinoid receptors (CBRs) exerted on the neurotoxicity of alcohol. Methods In this study, dynamic development of neuronal necroptosis in the PFC region was monitored after 95% (v/v) alcohol vapor administration for 15 and 30 days, respectively. Selective CBRs agonists or inverse agonists were pretreated according to the experimental design. All the PFC tissues were isolated and further examined by biochemical and histopathological analyses. Results It was found that chronic alcohol exposure increased the protein level of MLKL and also the phosphorylated levels of RIP1, RIP3 and MLKL in a time-dependent manner, all of which indicated the activation of necroptosis signaling. Particularly, compared to astrocytes, neurons from the PFC showed more prototypical necrotic morphology in response to alcohol insults. In parallel, an increased protein level of CB1R was also found after 15 and 30 days alcohol exposure. Administration of specific inverse agonists of CB1R (AM251 and AM281), but not its agonists or CB2R modulators, significantly alleviated the RIP1/RIP3/MLKL-mediated neuronal necroptosis. Conclusion We reported the involvement of RIP1/RIP3/MLKL-mediated necroptosis in alcohol-induced PFC neurotoxicity, and identified CB1R as a critical regulator of neuronal necroptosis that enhanced our understanding of alcohol-induced neuropathology in the PFC.


2014 ◽  
Vol 307 (9) ◽  
pp. G941-G949 ◽  
Author(s):  
Padmanabhan Srinivasan ◽  
Rubina Kapadia ◽  
Arundhati Biswas ◽  
Hamid M. Said

Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5′-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na+ dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms.


1976 ◽  
Vol 273 (1 Work in Progr) ◽  
pp. 205-211 ◽  
Author(s):  
Jack Wang ◽  
Mark Marvin ◽  
Bruce Abel ◽  
Richard N. Pierson

BioFactors ◽  
2018 ◽  
Vol 45 (2) ◽  
pp. 187-199 ◽  
Author(s):  
Zheng Xu ◽  
Can Wang ◽  
Xiaoguang Dong ◽  
Tao Hu ◽  
Lingling Wang ◽  
...  

2010 ◽  
Vol 3 ◽  
pp. 316-320 ◽  
Author(s):  
Wei Zhu ◽  
Yiqing Li ◽  
Richard M. Kream ◽  
George B. Stefano

2016 ◽  
Vol 22 (3) ◽  
pp. 766-778 ◽  
Author(s):  
Florence P. Varodayan ◽  
Michal Bajo ◽  
Neeraj Soni ◽  
George Luu ◽  
Samuel G. Madamba ◽  
...  

2017 ◽  
Vol 22 (8) ◽  
pp. 1079-1079 ◽  
Author(s):  
E Shokri-Kojori ◽  
D Tomasi ◽  
C E Wiers ◽  
G-J Wang ◽  
N D Volkow

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