Anthocyanins: Are They Beneficial in Treating Ethanol Neurotoxicity?

Chen, Gang; Luo, Jia

doi:10.1007/s12640-009-9083-4

Cited by 37 publications

(32 citation statements)

References 132 publications

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“…23,24 Ethanol causes oxidative stress in neurons in vitro and in vivo. 25 We have previously demonstrated that ethanol induces ROS generation in SH-SY5Y cells. 26 Antioxidants block ethanol-induced LC3 lipidation, suggesting that autophagy is activated in response to ethanol-induced oxidative stress.…”

Section: Discussionmentioning

confidence: 96%

Autophagy is a protective response to ethanol neurotoxicity

et al. 2012

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Section: Discussionmentioning

confidence: 96%

Autophagy is a protective response to ethanol neurotoxicity

et al. 2012

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“…31 Ethanol metabolism also causes lipid peroxidation, oxidative stress and ER dysfunction in liver, brain and other organs. 32 We have reported that chronic ethanol feeding to rodents mobilizes adaptive ER stress responses in exocrine pancreas involving the IRE1/XBP1 UPR branch. 6,33 In the absence of this adaptive response there is impaired early onset of protective IRE1/XBP1s signaling, and upregulation of the PERK/CHOP pathway that converge into ER dysfunction and acinar cell pathology that mimics several features of human alcoholic pancreatitis.…”

Section: Discussionmentioning

confidence: 97%

The Combination of Alcohol and Cigarette Smoke Induces Endoplasmic Reticulum Stress and Cell Death in Pancreatic Acinar Cells

Lugea

Gerloff

et al. 2017

Gastroenterology

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Background & Aims Smoking, an independent risk factor for pancreatitis, accelerates the development of alcoholic pancreatitis. Alcohol feeding of mice induces upregulation of spliced X-box binding protein 1 (XBP1s), which regulates the endoplasmic reticulum (ER) unfolded protein response and promotes cell survival upon ER stress. We examined whether smoking affects the adaptive mechanisms induced by alcohol and accelerates disorders of the ER in pancreatic acinar cells. Methods We studied the combined effects of ethanol and cigarette smoke extract (CSE) on ER-stress and cell death responses in mouse and human primary acini and the acinar cell line AR42J. Cells were incubated with ethanol (EtOH, 50 mM), CSE (20–40 μg/ml), or both (CSE+EtOH), and analyzed by immunoblotting, quantitative reverse transcription PCR, and cell death assays. Some cells were incubated with MKC-3946, an inhibitor of endoplasmic reticulum to nucleus signaling 1 (ERN1, also called IRE1) that blocks XBP1s formation. Male Sprague-Dawley rats were fed isocaloric amounts of an ethanol-containing (Lieber-DeCarli) or control diet for 11 weeks and exposed to cigarette smoke or room air in an exposure chamber for 2 hours each day. During the last 3 weeks, a subset of rats received intravenous injections of lipopolysaccharide (LPS, 3 mg/kg per weeks) to induce pancreatitis or saline (control). Pancreatic tissues were collected and analyzed by histology and immunostaining techniques. Results In AR42J and primary acini, CSE+EtOH induced cell death (necrosis and apoptosis), but neither agent alone had this effect. Cell death was associated with a significant decrease in expression of XBP1s. CSE+EtOH, but neither agent alone, slightly decreased ATP levels in AR42J cells, but induced oxidative stress and sustained activation (phosphorylation) of eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3, also called PERK) and increased protein levels of DNA damage inducible transcript 3 (DDIT3, also called CHOP). CHOP regulates transcription to promote apoptosis. Incubation of AR42J or primary mouse or human acinar cells with MKC-3946 reduced expression of XBP1s, increased levels of CHOP and induced cell death. In rats fed ethanol diet, exposure to cigarette smoke increased ER stress in acinar cells and sensitized the pancreas to LPS-induced pathology. Conclusions Cigarette smoke promotes cell death and features of pancreatitis in ethanol-sensitized acinar cells by suppressing the adaptive unfolded protein response signaling pathway. It also activates ER stress pathways that promote acinar cell death.

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“…58 In neurons, ethanol-induced ROS mainly come from damaged mitochondria and the activation of NOX (NADPH oxidase). [38][39][40]59 NOX-derived production of ROS activates autophagy. 57 Antioxidants partially block ethanol-induced autophagic flux and mitophagy, suggesting that ROS is involved in ethanol activation of autophagy.…”

Section: Oxidative Stressmentioning

confidence: 99%