Role of phosphatidylinositol 3-kinase in the development of hepatocyte preconditioning

Carini, Rita; Cesaris, Maria Grazia De; Splendore, Roberta; Baldanzi, Gianluca; Nitti, Mariapaola; Alchera, Elisa; Filigheddu, Nicoletta; Domenicotti, Cinzia; Pronzato, Maria Adelaide; Graziani, Andrea; Albano, Emanuele

doi:10.1053/j.gastro.2004.06.018

Cited by 62 publications

(99 citation statements)

References 37 publications

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“…12 It has been reported that E2 activates adenylate cyclase and induces cAMP/PKA signaling pathway via GPR30 in human keratinocytes 39 and breast cancer cells. 40 The PKA-dependent signaling pathway plays a key role in the development of hepatic tolerance to hypoxia/reperfusion 41 and mediates anti-apoptotic effects after ischemic liver injury. 18 Moreover, PKA can phosphorylate the prosurvival transcription factor CREB (cAMP response element-binding protein).…”

Section: Discussionmentioning

confidence: 99%

G Protein-Coupled Receptor 30-Dependent Protein Kinase A Pathway Is Critical in Nongenomic Effects of Estrogen in Attenuating Liver Injury after Trauma-Hemorrhage

Hsieh

Frink

et al. 2007

The American Journal of Pathology

102

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Although nongenomic effects of 17␤-estradiol (E2) are mediated via the estrogen receptor ␣ (ER-␣) , the existence of another novel ER , G protein-coupled receptor 30 (GPR30) , has been suggested as a candidate for triggering a broad range of E2-mediated signaling. GPR30 also acts independently of the ER to promote activation of the protein kinase A (PKA) pathway , which protects cells from apoptosis through Bcl-2. In this study , we examined whether the salutary effects of E2 in attenuating hepatic injury after trauma-hemorrhage are mediated via GPR30-or ER-␣-regulated activation of PKA-dependent signaling. At 2 hours after trauma-hemorrhage , administration of E2-conjugated to bovine serum albumin (E2-BSA , membrane impermeable) or E2 induced the up-regulation of ER-␣ and GPR30 and attenuated hepatic injury. This was accompanied by increases in PKA activity and Bcl-2 expression. Inhibition of PKA in E2-BSA-treated traumahemorrhage rats by PKA inhibitor H89 prevented the E2-BSA attenuation of hepatic injury. Isolated hepatocytes were transfected with small interfering RNA to suppress GPR30 or ER. We found that suppression of GPR30 but not ER-␣ prevented E2-BSAor E2-induced PKA activation and Bcl-2 expression. These results suggest that the nongenomic salutary effect of E2 in reducing hepatic injury after traumahemorrhage is mediated through the PKA-dependent pathway via GPR30 but not ER-␣. (Am J Pathol

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Section: Discussionmentioning

confidence: 99%

G Protein-Coupled Receptor 30-Dependent Protein Kinase A Pathway Is Critical in Nongenomic Effects of Estrogen in Attenuating Liver Injury after Trauma-Hemorrhage

Hsieh

Frink

et al. 2007

The American Journal of Pathology

102

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“…The adenosine stop signal is reversible so that after local injury has resolved, HSCs can respond to new chemokines in other locations. Additionally, hepatic ischemic preconditioning, which protects against fibrosis, is thought to involve adenosine by a mechanism wherein PKA phosphorylates A 2A R, which activates PI3K by coupling it with Galphaiprotein through Src [60]. This leads to downstream activation of PKB/Akt-mediated phosphorylation, which in turn inactivates the apoptosis promoting-factor BAD and glycogen synthetase kinase 3 [60].…”

Section: Unique Aspects Of Adenosine Receptor Signaling In Organ Fibrmentioning

confidence: 99%

Signaling pathways involving adenosine A2A and A2B receptors in wound healing and fibrosis

Shaikh

Cronstein

2016

Purinergic Signalling

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Collagen and matrix deposition by fibroblasts is an essential part of wound healing but also contributes to pathologic remodeling of organs leading to substantial morbidity and mortality. Adenosine, a small molecule generated extracellularly from adenine nucleotides as a result of direct stimulation, hypoxia, or injury, acts via a family of classical sevenpass G protein-coupled protein receptors, A 2A and A 2B , leading to generation of cAMP and activation of downstream targets such as PKA and Epac. These effectors, in turn, lead to fibroblast activation and collagen synthesis. The regulatory actions of these receptors likely involve multiple interconnected pathways, and one of the more interesting aspects of this regulation is opposing effects at different levels of cAMP generated. Additionally, adenosine signaling contributes to fibrosis in organ-specific ways and may have opposite effects in different organs. The development of drugs that selectively target these receptors and their signaling pathways will disrupt the pathogenesis of fibrosis and slow or arrest the progression of the important diseases they underlie.

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“…Src-TYK can phosphorylate the EGF receptor and lead to its transactivation (8,23,64). cAMP and CPT-2-Me-cAMP have been shown to transactivate growth factor receptors as well (3,4,47,63).…”

Section: Camp-gef-mediated Cytoprotection Is Src Tyrosine Kinase Depementioning

confidence: 99%

cAMP-GEF cytoprotection by Src tyrosine kinase activation of phosphoinositide-3-kinase p110 β/α in rat hepatocytes

Gates¹,

Hohenester²,

Anwer³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Role of phosphatidylinositol 3-kinase in the development of hepatocyte preconditioning

Cited by 62 publications

References 37 publications

G Protein-Coupled Receptor 30-Dependent Protein Kinase A Pathway Is Critical in Nongenomic Effects of Estrogen in Attenuating Liver Injury after Trauma-Hemorrhage

G Protein-Coupled Receptor 30-Dependent Protein Kinase A Pathway Is Critical in Nongenomic Effects of Estrogen in Attenuating Liver Injury after Trauma-Hemorrhage

Signaling pathways involving adenosine A2A and A2B receptors in wound healing and fibrosis

cAMP-GEF cytoprotection by Src tyrosine kinase activation of phosphoinositide-3-kinase p110 β/α in rat hepatocytes

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