Anti-Apoptotic Pro-Survival Effect of Clotrimazole in a Normothermic Ischemia Reperfusion Injury Animal Model

Iannelli, Antonio; Sousa, George de; Zucchini, N; Saint-Paul, M; Gugenheim, Jean; Rahmani, Roger

doi:10.1016/j.jss.2010.03.035

Cited by 12 publications

(8 citation statements)

References 31 publications

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“…Clotrimazole (CLT) is an inhibitor of Ca 2+ -sensitive K + -channels that has been proposed as an antiapoptotic agent 36 , 37 . Clotrimazole, which inhibits lead-induced phosphatidylserine flip-flop (Fig.…”

Section: Resultsmentioning

confidence: 99%

Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells

Ahyayauch

García-Arribas

Sot

et al. 2018

Sci Rep

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The mechanisms of Pb(II) toxicity have been studied in human red blood cells using confocal microscopy, immunolabeling, fluorescence-activated cell sorting and atomic force microscopy. The process follows a sequence of events, starting with calcium entry, followed by potassium release, morphological change, generation of ceramide, lipid flip-flop and finally cell lysis. Clotrimazole blocks potassium channels and the whole process is inhibited. Immunolabeling reveals the generation of ceramide-enriched domains linked to a cell morphological change, while the use of a neutral sphingomyelinase inhibitor greatly delays the process after the morphological change, and lipid flip-flop is significantly reduced. These facts point to three major checkpoints in the process: first the upstream exchange of calcium and potassium, then ceramide domain formation, and finally the downstream scramblase activation necessary for cell lysis. In addition, partial non-cytotoxic cholesterol depletion of red blood cells accelerates the process as the morphological change occurs faster. Cholesterol could have a role in modulating the properties of the ceramide-enriched domains. This work is relevant in the context of cell death, heavy metal toxicity and sphingolipid signaling.

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Section: Resultsmentioning

confidence: 99%

Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells

Ahyayauch

García-Arribas

Sot

et al. 2018

Sci Rep

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“…JNK is activated in response to stress and inflammatory stimuli [18,37,95]. Numerous studies using experimental models of either warm or cold ischemia have demonstrated an injurious role of JNK activation in I-R injury in steatotic and non-steatotic livers [34,40,47,72,74,75,78,80,95,96,97,98,99,100,101,102,103]. Experimental data indicate that JNK is activated by TNF-α and IL-1, major mediators of hepatic I-R injury.…”

Section: Role Of Mapks In Experimental Models Of Hepatic I-r Injurmentioning

confidence: 99%

“…Hormones and growth factors such as the insulin-like growth factor (IGF), platelet-derived growth factor (PDGF) or EGF are the major regulators of ERK 1/2, but it also may be activated by cytokines, proteins of extracellular matrix such as fibronectin and collagen, glucose and ROS [41,42,110]. Although activation of ERK 1/2 has been mainly associated with cell proliferation and differentiation, there are studies indicating their potential involvement in hepatic I-R injury [7,46,50,80,95,97,98,99,100,111,112,113,114] (Table 5 and Table 6, Figure 1). However, a specific activator or inhibitor of ERK has not been used in any of these studies.…”

Section: Role Of Mapks In Experimental Models Of Hepatic I-r Injurmentioning

confidence: 99%

“…As previously mentioned in the case of JNK or p38, due to the lack of studies evaluating the effects of a specific activator or inhibitor of ERK 1/2 in hepatic I-R, it is unclear whether ERK 1/2 could be a potential therapeutic target in hepatic I-R injury. However, it has been demonstrated that protection against I-R injury afforded by several pharmacological strategies in steatotic and non-steatotic livers were associated with changes in ERK activation [7,46,50,80,95,97,98,99,100,111,112,113,114].…”

Section: Role Of Mapks In Experimental Models Of Hepatic I-r Injurmentioning

confidence: 99%

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Mitogen Activated Protein Kinases in Steatotic and Non-Steatotic Livers Submitted to Ischemia-Reperfusion

Jiménez‐Castro¹,

Cornide‐Petronio

Gracia‐Sancho

et al. 2019

IJMS

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: We analyzed the participation of mitogen-activated protein kinases (MAPKs), namely p38, JNK and ERK 1/2 in steatotic and non-steatotic livers undergoing ischemia-reperfusion (I-R), an unresolved problem in clinical practice. Hepatic steatosis is a major risk factor in liver surgery because these types of liver tolerate poorly to I-R injury. Also, a further increase in the prevalence of steatosis in liver surgery is to be expected. The possible therapies based on MAPK regulation aimed at reducing hepatic I-R injury will be discussed. Moreover, we reviewed the relevance of MAPK in ischemic preconditioning (PC) and evaluated whether MAPK regulators could mimic its benefits. Clinical studies indicated that this surgical strategy could be appropriate for liver surgery in both steatotic and non-steatotic livers undergoing I-R. The data presented herein suggest that further investigations are required to elucidate more extensively the mechanisms by which these kinases work in hepatic I-R. Also, further researchers based in the development of drugs that regulate MAPKs selectively are required before such approaches can be translated into clinical liver surgery.

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“…Beyond regulating gene transcription and detoxification processes, the PXR has recently been linked to the regulation of cell migration [36], cell survival [37, 38] apoptosis[37–39] and autophagy [39]. These effects have been attributed to the PXR’s interaction with p38 MAPK [36], JNK1/2 [40, 41]and AMPK [42]. Interestingly, each of these signaling cascades regulates key functions of IECs that contribute to intestinal mucosal barrier function.…”

Section: Intestinal Barrier Function and Ibdmentioning

confidence: 99%

Xenobiotic Receptor-Mediated Regulation of Intestinal Barrier Function and Innate Immunity

Ranhotra

Flannigan

Brave

et al. 2016

Nuclear Receptor Research

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The molecular basis for the regulation of the intestinal barrier is a very fertile research area. A growing body of knowledge supports the targeting of various components of intestinal barrier function as means to treat a variety of diseases, including the inflammatory bowel diseases. Herein, we will summarize the current state of knowledge of key xenobiotic receptor regulators of barrier function, highlighting recent advances, such that the field and its future are succinctly reviewed. We posit that these receptors confer an additional dimension of host-microbe interaction in the gut, by sensing and responding to metabolites released from the symbiotic microbiota, in innate immunity and also in host drug metabolism. The scientific evidence for involvement of the receptors and its molecular basis for the control of barrier function and innate immunity regulation would serve as a rationale towards development of non-toxic probes and ligands as drugs.

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Anti-Apoptotic Pro-Survival Effect of Clotrimazole in a Normothermic Ischemia Reperfusion Injury Animal Model

Cited by 12 publications

References 31 publications

Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells

Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells

Mitogen Activated Protein Kinases in Steatotic and Non-Steatotic Livers Submitted to Ischemia-Reperfusion

Xenobiotic Receptor-Mediated Regulation of Intestinal Barrier Function and Innate Immunity

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