Ethanol and Lipid Metabolic Signaling

Shukla, Shivendra D.; Sun, Grace Y.; Wood, W. Gibson; Savolainen, Markku J.; Alling, Christer; Hoek, Jan B.

doi:10.1111/j.1530-0277.2001.tb02370.x

Cited by 21 publications

(8 citation statements)

References 47 publications

(42 reference statements)

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“…It is well established that membrane components represent cellular targets of alcohol action. Ethanol-induced alteration of membrane lipids (Shukla et al 2001) might affect the sphingomyelin/ceramide ratio, activating different response elements which may initiate the pathways of cell death (Tepper et al 2000;Mimeault 2002). Recent studies also demonstrated the importance of ceramide generation within caveolae and rafts, which contain diverse signalling response elements (Cremesti et al 2002;Mimeault 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Activation of N-SMase or A-SMase within the rafts, in response to stress signals, leads to ceramide generation and raft reorganization, facilitating receptor aggregation and the activation of different signalling pathways (Cremesti et al 2002). Ethanol, through its interaction with membrane lipids (Shukla et al 2001), might also induce changes in raft sphingolipids, affecting N/A-SMase and ceramide generation, and promoting the activation of different signalling processes. Alternatively, ethanol induces oxidative stress in astrocytes (Montoliu et al 1995), and several lines of evidence suggest that free radical species and oxidative stress can activate the sphingomyelin-ceramide pathway and apoptotic cell death (Andrieu-Abadie et al 2001).…”

Section: Discussionmentioning

confidence: 99%

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Ceramide pathways modulate ethanol‐induced cell death in astrocytes

Pascual¹,

Valles²,

Renau‐Piqueras

et al. 2003

Journal of Neurochemistry

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We showed previously that alcohol exposure during in vivo brain development induced astroglial damage and caused cell death. Because ceramide modulates a number of biochemical and cellular responses to stress, including apoptosis, we now investigate whether ethanol-induced cell death in astrocytes is mediated by ceramide signalling pathways triggering apoptosis. Here we show that both ethanol and ceramide are able to induce apoptotic death in cultured astrocytes, in a dosedependent manner, and that C 2 -ceramide addition potentiates the apoptotic effects of ethanol. Cell death induced by ethanol is associated with stimulation of neutral and acidic sphingomyelinase (SMase) and ceramide generation, as well as with activation of stress-related kinases, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38) and extracellular signal-regulated kinase (ERK) pathways. We also provide evidence for the participation of JNK and p38 in ethanol-induced cell death, because pharmacological inhibitors of these kinases largely prevent the apoptosis induced by ethanol or by ethanol and C 2 -ceramide. Furthermore, we show that ethanol-induced ERK activation triggers the stimulation of cyclo-oxygenase-2 (COX-2) and the release of prostaglandin E 2 , and that blockade of the mitogen-activated protein kinase kinase (MEK)/ERK pathway by PD98059 abolishes the up-regulation of COX-2 induced by ethanol plus ceramide, and decreases the ethanol-induced apoptosis. These results strongly suggest that ethanol is able to stimulate the SMase-ceramide pathway, leading to the activation of signalling pathways implicated in cell death. These findings provide an insight into the mechanisms involved in ethanolinduced astroglial cell death during brain development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ceramide pathways modulate ethanol‐induced cell death in astrocytes

Pascual¹,

Valles²,

Renau‐Piqueras

et al. 2003

Journal of Neurochemistry

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“…For example, many studies demonstrate that ethanol exposure can enhance or suppress protein kinase C, a signaling pathway that is important in endothelial cell responses, depending on the dose of ethanol [79,80]. Ethanol has also been implicated in membranelipid remodeling, lipid-derived signals, and production of lipid mediators [81]. One study determined that 5% of membrane phospholipids was phosphatidylethanol in ethanol-treated endothelial cells, compared with only 0.5-1% in those cells not treated with ethanol.…”

Section: Acute Ethanol and Wound Angiogenesismentioning

confidence: 98%

Brewing complications: the effect of acute ethanol exposure on wound healing

Radek

Ranzer

DiPietro

2009

Journal of Leukocyte Biology

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Ethanol consumption is linked to a higher incidence of traumatic wounds and increases the risk for morbidity and mortality following surgical or traumatic injury. One of the most profound effects of acute ethanol exposure on wound healing occurs during the inflammatory response, and altered cytokine production is a primary component. Acute ethanol exposure also impairs the proliferative response during healing, causing delays in epithelial coverage, collagen synthesis, and blood vessel regrowth. The accumulated data support the paradigm that acute ethanol intoxication prior to injury significantly diminishes a patient's ability to heal efficiently.

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“…We have recently revealed the molecular structure of novel endogenous DHA‐derived 14 S ,21‐di‐hydroxy‐docosa‐4 Z ,7 Z ,10 Z ,12 E ,16 Z ,19 Z ‐hexaenoic acid (14 S ,21‐diHDHA) in skin wounds and found that it is a reparative lipid mediator (LM) that promotes wound healing [Lu et al, 2010]. It has been known that AE dysregulates the biosynthesis of LMs [Shukla et al, 2001; Molina, 2008; Sozio and Crabb, 2008]. However, there are no reports regarding the roles of LMs in AE‐impaired wound healing and angiogenesis, no mention of 14 S ,21‐diHDHA.…”

mentioning

confidence: 99%

Novel 14S,21‐dihydroxy‐docosahexaenoic acid rescues wound healing and associated angiogenesis impaired by acute ethanol intoxication/exposure

Tian

Lü

Shah

et al. 2010

J of Cellular Biochemistry

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Acute ethanol intoxication and exposure (AE) has been known to impair wound healing and associated angiogenesis. Here we found that AE diminished the formation of novel reparative lipid mediator 14S,21-dihydroxy-docosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S,21-diHDHA) and its biosynthetic intermediate 14S-hydroxy-DHA (14S-HDHA) from docosahexaenoic acid (DHA) in murine wounds. However, AE did not reduce the formation of DHA and the intermediate 21-HDHA. These results indicate that in the biosynthetic pathways of 14S,21-diHDHA in wounds, AE suppresses the 14S-hydroxy-generating activity of 12-lipoxygenase-like (LOX-like), but does not suppress the 21-hydroxy-generating activity of cytochrome P450 and DHA-generating activities. The AE-suppression of 12-LOX-like activity was further confirmed by the diminished formation of 12-hydroxy-eicosatetraenoic acid in wounds under AE. Supplementing 14S,21-diHDHA to wounds rescued the AE-impaired healing and vascularization. 14S,21-diHDHA restored AE-impaired processes of angiogenesis in vitro: endothelial cell migration, tubulogenesis, and phosphorylation of p38 mitogen-activated protein kinase (MAPK). Taken together, the suppression of 14S,21-diHDHA formation is responsible, at least partially, for the AE-impairment of cutaneous wound healing and angiogenesis. Supplementing 14S,21-diHDHA to compensate its deficit in AE-impaired wounds rescues the healing and angiogenesis. These results provide a novel mechanistic insight for AE-impaired wound healing that involves the necessary roles of 14S,21-diHDHA. They also offer leads for developing 14S,21-diHDHA-related therapeutics to ameliorate AE-impairment of wound healing.

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Ethanol and Lipid Metabolic Signaling

Cited by 21 publications

References 47 publications

Ceramide pathways modulate ethanol‐induced cell death in astrocytes

Ceramide pathways modulate ethanol‐induced cell death in astrocytes

Brewing complications: the effect of acute ethanol exposure on wound healing

Novel 14S,21‐dihydroxy‐docosahexaenoic acid rescues wound healing and associated angiogenesis impaired by acute ethanol intoxication/exposure

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