The MAP kinase cascades are activated during post‐ischemic liver reperfusion

Bendinelli, Paola; Piccoletti, Roberta; Maroni, Paola; Bernelli‐Zazzera, Aldo

doi:10.1016/s0014-5793(96)01228-8

Cited by 71 publications

(66 citation statements)

References 43 publications

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“…Among the most proximal events in liver I/R is MAPK activation. 28,29 Cisplatin can affect MAPK signaling 14 ; therefore, to determine whether cisplatin alters liver I/R-induced MAPK activation, western blots for JNK, ERK, and p38 were performed on livers from mice that had undergone I/R. As before, mice were pretreated 12 hours prior with either NSS or cisplatin.…”

Section: Resultsmentioning

confidence: 99%

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Cisplatin prevents high mobility group box 1 release and is protective in a murine model of hepatic ischemia/reperfusion injury

et al. 2009

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The nuclear protein high mobility group box 1 (HMGB1) is an important inflammatory mediator involved in the pathogenesis of liver ischemia/reperfusion (I/R) injury. Strategies aimed at preventing its release from stressed or damaged cells may be beneficial in preventing inflammation after I/R. Cisplatin is a member of the platinating chemotherapeutic agents and can induce DNA lesions that are capable of retaining high mobility group proteins inside the nucleus of cells. In vitro studies in primary cultured rat hepatocytes show that nontoxic concentrations of cisplatin can sequester HMGB1 inside the nucleus of hypoxic cells. Similarly, the in vivo administration of nontoxic doses of cisplatin prevents liver damage associated with a well-established murine model of hepatic I/R as measured by lower circulating serum aminotransferase levels, lower hepatic inflammatory cytokine levels including tumor necrosis factor ␣ and interleukin-6, lower inducible NO synthase expression, and fewer I/R-associated histopathologic changes. The mechanism of action in vivo appears to involve the capacity of cisplatin to prevent the I/R-induced release of HMGB1 as well as to alter cell survival and stress signaling in the form of autophagy and mitogen-activated protein kinase activation, respectively. Conclusion: Low, nontoxic doses of cisplatin can sequester HMGB1 inside the nucleus of redox-stressed hepatocytes in vitro and prevent its release in vivo in a murine model of hepatic I/R. Furthermore, cell survival and stress signaling pathways are altered by low-dose cisplatin. Therefore, platinating agents may provide a novel approach to mitigating the deleterious effects of I/R-mediated disease processes. (HEPATOLOGY 2009;50:565-574.)

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Section: Resultsmentioning

confidence: 99%

“…15 MAPK activation contributes to the inflammatory response following liver I/R. 28,29 Therefore, we examined whether cisplatin alters liver I/R-induced MAPK activation. We found that cisplatin blunts I/R-induced JNK and p38 activation.…”

Section: Discussionmentioning

confidence: 99%

Cisplatin prevents high mobility group box 1 release and is protective in a murine model of hepatic ischemia/reperfusion injury

et al. 2009

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“…It includes SAPKs, which are the target of environmental stress, such as liver ischemia-reperfusion. 12,20,21 Among this group, JNK 1 /SAPK 1 is known to be stimulated in vivo after rat liver transplantation 21 or partial hepatectomy. 46 However, these stress conditions also stimulate TNF-␣, which is known to activate JNKs.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that ischemia and reperfusion could modulate MAPK activity in perfused rat heart, 40 in rat liver, 20 and in rat hepatocytes after liver transplantation. 21 On the basis of these observations, we became interested in studying the effect of hypoxia-reoxygenation (H/R) stress on the different members of endogenous SAPKs in primary cultured rat hepatocytes.…”

Section: Warm Hypoxia-reoxygenation Of Hepatocytes Differently Modulamentioning

confidence: 99%

Protein Kinase Activation by Warm And Cold Hypoxia- Reoxygenation in Primary-Cultured Rat Hepatocytes–JNK1/SAPK1 Involvement in Apoptosis

et al. 2000

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Ischemia-reperfusion procedures induced severe hepatic damages owing to different processes related to hypoxia and reoxygenation (H/R) phases, including the consecutive oxygen free radical (OFR) release. Stress-activated protein kinases (SAPKs) could be activated by extracellular stimuli. The aim of this study was to show whether H/R stress conditions could stimulate these kinases, and especially c-jun-N-terminal kinase (JNK 1 /SAPK 1 ), to reveal a potential role of JNK 1 /SAPK 1 in the control of hepatocyte apoptosis. Primary cultured rat hepatocytes, isolated from other liver cells and blood flow, were subjected to warm and cold hypoxiareoxygenation phases mimicking surgical and transplant conditions. The activation status of SAPKs was evaluated by immunoprecipitation or Western-blotting experiments, whereas apoptosis was assessed by measuring caspase activation and internucleosomal DNA fragmentation in vitro and by TUNEL reaction, in vivo. Hypoxia, and especially hypoxia-reoxygenation, significantly increased JNK 1 /SAPK 1 activation in cultured hepatocytes. Either in warm or cold conditions, OFR scavengers (N-Acetylcystein, Di-Phenyleneiodonium, Deferoxamine) decreased this stimulation. Warm ischemia-reperfusion also led to JNK activation. Hypoxia and especially hypoxia-reoxygenation induced programmed cell death in vivo and in vitro. This last phenomenon was inhibited when hepatocytes were treated with SB 202190, which was described as a potent inhibitor of p38 and JNK activities. Altogether, these results confirmed that JNK 1 /SAPK 1 was activated during the hypoxia-reoxygenation process, and that this activity participated in the onset of the apoptosis program. (HEPATOLOGY 2000;32:1029-1036.)

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“…In a number of cell types, heat shock apparently fails to activate ERK MAPKs but does activate the stress-activated MAPKs such as the JNK MAPKs (3,38). However, these responses are apparently cell type-dependent, and heat shock prevents activation of JNK MAPKs and p38 MAPKs in U937 cells but does activate ERK MAPKs in H56 hepatoma cells, NIH 3T3 fibroblasts, human HeLa cells, human KB carcinoma cells, or during whole animal hyperthermia (41)(42)(43)(44)(45). In all of these examples, the activation of ERK MAPK was not examined beyond an initial 60 min of heat shock, and so any long term effect on signaling pathways was not evaluated.…”

Section: Discussionmentioning

confidence: 99%

The Mechanism of Heat Shock Activation of ERK Mitogen-activated Protein Kinases in the Interleukin 3-dependent ProB Cell Line BaF3

Bogoyevitch

2000

Journal of Biological Chemistry

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We have investigated heat shock stimulation of MAPK cascades in an interleukin 3-dependent cell line, BaF3. Following exposure to 42°C, the stress-activated JNK MAPKs were phosphorylated and activated, but p38 MAPKs remained unaffected. Surprisingly, heat shock also activated ERK MAPKs in a potent (>60-fold), delayed (>30 min), and sustained (>120 min) manner. These characteristics suggested a novel mechanism of ERK MAPK activation and became the focus of this study. A MEK-specific inhibitor, PD98059, inhibited heat shock ERK MAPK activation by >75%. Surprisingly, a role for Ras in the heat shock response was eliminated by the failure of a dominant-negative Ras Asn-17 mutant to inhibit ERK MAPK activation and the failure to observe increases in Ras⅐GTP. Heat shock also failed to stimulate activation of A-, B-, and c-Raf. Instead, a serine/threonine phosphatase inhibitor, okadaic acid, activated ERK MAPK in a similar manner to heat shock. Furthermore, pretreatment with suramin, generally recognized as a broad range inhibitor of growth factor receptors, inhibited both okadaic acid-stimulated and heat shock-stimulated ERK MAPK activity by >40%. Inhibiting ERK MAPK activation during heat shock with PD98059 enhanced losses in cell viability. These results demonstrate Ras-and Raf-independent ERK MAPK activation maintains cell viability following heat shock.

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The MAP kinase cascades are activated during post‐ischemic liver reperfusion

Cited by 71 publications

References 43 publications

Cisplatin prevents high mobility group box 1 release and is protective in a murine model of hepatic ischemia/reperfusion injury

Cisplatin prevents high mobility group box 1 release and is protective in a murine model of hepatic ischemia/reperfusion injury

Protein Kinase Activation by Warm And Cold Hypoxia- Reoxygenation in Primary-Cultured Rat Hepatocytes–JNK1/SAPK1 Involvement in Apoptosis

The Mechanism of Heat Shock Activation of ERK Mitogen-activated Protein Kinases in the Interleukin 3-dependent ProB Cell Line BaF3

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