Protein kinase C-dependent activation of P44/42 mitogen-activated protein kinase and heat shock protein 70 in signal transduction during hepatocyte ischemic preconditioning

Gao, Yi; Shan, Yuqiang; Pan, Mingxin; Wang, Yu; Tang, Lijun; Li, Hao; Zhi, Zhang

doi:10.3748/wjg.v10.i7.1019

Cited by 17 publications

(15 citation statements)

References 51 publications

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“…Both pathways ERK and the Akt are prosurvival and are activated in stable diabetes but not in the development stage. Minor damage of hepatocytes in stable diabetes correlated with �inding that a rapid activation of P44/42 ERK participates in the preservation of liver cells [38]. Hence, it was suggested that the balance between magnitude of ERK and JNK activation was the key to determining survival or death of the cells [39].…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Activation Level of JNK and Akt/ERK Signaling Pathways Determinates Extent of DNA Damage in the Liver of Diabetic Rats

Martinović

Grigorov

Bogojević³

et al. 2012

Cell Physiol Biochem

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Aims: Diabetes-related oxidative stress conditions lead to progressive tissue damage and disfunctionality. Mechanisms underlying liver pathophysiology during diabetes are not fully understood. The aim of this study was to find relationship between diabetes-related DNA damage in the rat liver and activities of prosurvival signaling pathways. Methods: Effect of diabetes was analyzed two (development stage) and eight weeks (stable diabetes) after single intraperitoneal injection of streptozotocin. Extent of DNA damage, analysed by comet assay, was corelated with oxidative status (plasma level of ROS, liver antioxidant capacity) and activity/abundance of kinases (Akt, p38, ERK1, JNK, JAK) and transcription factors NF-ĸB p65 and STAT3. Results: Significant DNA damage in development stage is accompanied by elevated plasma levels of O₂^-and H₂O₂, decreased activities of CAT, MnSOD, and GST in the liver and increased activation of proapoptotic JNK signal pathway. Lower DNA damage in stable diabetes, is accompanied by elevated plasma level of O₂^-, restored antioxidative liver enzyme activity, decreased activation of JNK and increased activation of prosurvival Akt and ERK signal pathways. Conclusion: These findings indicate that level of DNA damage in diabetic liver depends on the extent of oxidative stress, antioxidant activity and balance between JNK and Akt/ERK signal pathways activation.

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Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Activation Level of JNK and Akt/ERK Signaling Pathways Determinates Extent of DNA Damage in the Liver of Diabetic Rats

Martinović

Grigorov

Bogojević³

et al. 2012

Cell Physiol Biochem

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“…It has been reported that PKC can be induced by hypoxia (3,6,22). Our data show that the expression and plasma membrane translocation of PKC is activated by hypoxia in MLEC, which preferentially involved the ␣ and isoforms (Fig.…”

mentioning

confidence: 58%

FLIP Protects against Hypoxia/Reoxygenation-Induced Endothelial Cell Apoptosis by Inhibiting Bax Activation

Wang

Zhang

et al. 2005

Molecular and Cellular Biology

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Hypoxia/reoxygenation causes cell death, yet the underlying regulatory mechanisms remain partially understood. Recent studies demonstrate that hypoxia/reoxygenation can activate death receptor and mitochondria-dependent apoptotic pathways, involving Bid and Bax mitochondrial translocation and cytochrome c release. Using mouse lung endothelial cells (MLEC), we examined the role of FLIP, an inhibitor of caspase 8, in hypoxia/reoxygenation-induced cell death. FLIP protected MLEC against hypoxia/reoxygenation by blocking both caspase 8/Bid and Bax/mitochondrial apoptotic pathways. FLIP inhibited Bax activation in wild-type and Bid−/− MLEC, indicating independence from the caspase 8/Bid pathway. FLIP also inhibited the expression and activation of protein kinase C (PKC) (α, ζ) during hypoxia/reoxygenation and promoted an association of inactive forms of PKC with Bax. Surprisingly, FLIP expression also inhibited death-inducing signal complex (DISC) formation in the plasma membrane and promoted the accumulation of the DISC in the Golgi apparatus. FLIP expression also upregulated Bcl-XL, an antiapoptotic protein. In conclusion, FLIP decreased DISC formation in the plasma membrane by blocking its translocation from the Golgi apparatus and inhibited Bax activation through a novel PKC-dependent mechanism. The inhibitory effects of FLIP on Bax activation and plasma membrane DISC formation may play significant roles in protecting endothelial cells from the lethal effects of hypoxia/reoxygenation

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“…A number of reports have indicated that protein kinase C was critical for the development of IPC in rat, rabbit and human myocardiocytes [179,180] . Gao and associates showed that the activation of protein kinase C and its downstream ERK-1/2 mediators were increased in IPC-treated in vivo and in vitro models [163] . Data from this study also suggested that the expression of HSP70 was reduced and the protective effect of IPC was diminished when ERK-1/2 activity was reduced by a MAPK inhibitor (PD-98059).…”

Section: Activation Of Downstream Mitogen-activated Protein Kinases (mentioning

confidence: 99%

“…Studies have shown that protein kinase C plays a pivotal role in the activation of ERK-1/2 signaling pathway [163,178] that participates in the preservation of hepatocytes [163] . A number of reports have indicated that protein kinase C was critical for the development of IPC in rat, rabbit and human myocardiocytes [179,180] .…”

Section: Activation Of Downstream Mitogen-activated Protein Kinases (mentioning

confidence: 99%

“…IPC induces over-expression of HSP 70 in isolated hepatocytes [163] , and reduces liver IL-1 synthesis under normothermic conditions [164] . Besides expressing cytoprotective effects [165,166] , HSP induction leads to the down-regulation of IL-1 synthesis in pancreatic [161,167] and lung [162,168] cell studies.…”

Section: Down-regulation Of Inhibitory Mediators Of Liver Regenerationmentioning

confidence: 99%

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Role of ischaemic preconditioning in liver regeneration following major liver resection and transplantation

Gomez¹

2007

WJG

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Liver ischaemic preconditioning (IPC) is known to protect the liver from the detrimental effects of ischaemicreperfusion injury (IRI), which contributes significantly to the morbidity and mortality following major liver surgery. Recent studies have focused on the role of IPC in liver regeneration, the precise mechanism of which are not completely understood. This review discusses the current understanding of the mechanism of liver regeneration and the role of IPC in this setting. Relevant articles were reviewed from the published literature using the Medline database. The search was performed using the keywords "liver", "ischaemic reperfusion", "ischaemic preconditioning", "regeneration", "hepatectomy" and "transplantation". The underlying mechanism of liver regeneration is a complex process involving the interaction of cytokines, growth factors and the metabolic demand of the liver. IPC, through various mediators, promotes liver regeneration by up-regulating growthpromoting factors and suppresses growth-inhibiting factors as well as damaging stresses. The increased understanding of the cellular mechanisms involved in IPC will enable the development of alternative treatment modalities aimed at promoting liver regeneration following major liver resection and transplantation.

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Protein kinase C-dependent activation of P44/42 mitogen-activated protein kinase and heat shock protein 70 in signal transduction during hepatocyte ischemic preconditioning

Cited by 17 publications

References 51 publications

Activation Level of JNK and Akt/ERK Signaling Pathways Determinates Extent of DNA Damage in the Liver of Diabetic Rats

Activation Level of JNK and Akt/ERK Signaling Pathways Determinates Extent of DNA Damage in the Liver of Diabetic Rats

FLIP Protects against Hypoxia/Reoxygenation-Induced Endothelial Cell Apoptosis by Inhibiting Bax Activation

Role of ischaemic preconditioning in liver regeneration following major liver resection and transplantation

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