Inhibition of hypoxia/reoxygenation-induced oxidative stress in HGF-stimulated antiapoptotic signaling: role of PI3-K and Akt kinase upon rac1

Ozaki, Michitaka; Haga, Sanae; Zhang, H Q; Irani, Kaikobad; Suzuki, Seiichi

doi:10.1038/sj.cdd.4401172

Cited by 106 publications

(84 citation statements)

References 39 publications

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“…In a liver IRI rat model, pre-treatment with HGF inhibited the production of reactive oxygen species and its damaging effects [176] . Similar results were observed in a hypoxia-reoxygenation-induced oxidative stress model in hepatocytes [177] . These results suggest that the anti-apoptotic effect of HGF could pave the way for hepatocyte proliferation following IRI.…”

Section: Increased Production Of Growth Factorssupporting

confidence: 86%

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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Section: Increased Production Of Growth Factorssupporting

confidence: 86%

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

Gomez¹

2007

WJG

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“…19,21,30 In this study, knockdown of p66 Shc phosphorylated/activated Akt in the post-PH liver, similarly to the young mice. As Akt is known as an anti-oxidant/prosurvival molecule, [31][32][33] Akt activation immediately after PH resulting from p66 Shc knockdown may have a major function in suppressing post-PH OS/apoptosis and injury in the post-PH liver of aged mice.…”

Section: Discussionmentioning

confidence: 99%

p66Shc has a pivotal function in impaired liver regeneration in aged mice by a redox-dependent mechanism

Haga

Morita

Irani

et al. 2010

Laboratory Investigation

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Liver regeneration involves complicated processes and is affected by various patho-physiological conditions. This study was designed to examine the molecular mechanisms underlying the aging-associated impairment of liver regeneration. Male C57BL/6J mice were used as young and aged mice (o10 weeks and 420 months old, respectively). These mice were subjected to 70% partial hepatectomy (PH). Liver regeneration and liver injury/stresses were evaluated chronologically after PH. Post-hepatectomy liver regeneration was markedly impaired in aged mice. Though the extent of hepatocyte proliferation in the regenerating liver was similar in aged and young mice, cell growth was absent in aged mice. Oxidative stress (OS) was observed immediately after hepatectomy, followed by marked apoptosis in aged mice. Signaling molecules regarding cell proliferation (mitogen-activated protein kinase, STAT3, p46/52 Shc ) and anti-oxidation (catalase, superoxide dismutase, Ref-1, glutathione peroxidase) were expressed/activated after hepatectomy in livers of both aged and young mice. Akt was not activated in aged-mouse liver, but its expression was similar to that in young mice. p66 Shc , known as an age-/oxidantassociated protein, was strongly phosphorylated. By knocking down p66 Shc , the impairment of liver regeneration was normalized. OS immediately after hepatectomy induced subsequent liver injury (apoptosis), and deletion of p66 Shc suppressed both OS and hepatocyte apoptosis in the regenerating liver of aged mice. Though we need additional data in other animal models to fully understand the mechanism, p66 Shc may have a pivotal function in the impairment of liver regeneration in aged mice by triggering OS and subsequent apoptosis. This data may provide a clue to understanding the mechanism underlying the association between aging and the impairment of liver regeneration.

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“…31 HGF also prevented hippocampal cell death in rats with transient forebrain ischemia 32 through phosphorylation of extracellular signal-regulated kinase. Since PI3-K/Akt inhibits reactive oxygen species production through rac1, 32,33 HGF might reduce oxidative stress through the PI3-K/Akt pathway. In this study, we also evaluated the phosphorylation of Akt and MAPK by western blotting.…”

Section: Discussionmentioning

confidence: 99%

Alleviation of Aβ-induced cognitive impairment by ultrasound-mediated gene transfer of HGF in a mouse model

et al. 2008

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A new therapeutic approach to treat Alzheimer's disease (AD) is needed, and the use of growth factors is considered to be a candidate. Hepatocyte growth factor (HGF) is a unique multifunctional growth factor, which has the potential effect to exert neurotrophic action and induce angiogenesis. In this study, we examined the effects of overexpression of human HGF plasmid DNA using ultrasound-mediated gene transfer into the brain in an Ab-infused cognitive dysfunction mouse model. We demonstrated that HGF gene transfer significantly alleviated Ab-induced cognitive impairment in mice in behavioral tests. These beneficial effects of HGF might be due to (1) significant recovery of the vessel density in the dentate gyrus of the hippocampus, (2) upregulation of BDNF, (3) a significant decrease in oxidative stress and (4) synaptic enhancement. A pharmacological approach including gene therapy to increase the HGF level in combination with anti-Ab therapy might be a new therapeutic option for the treatment of AD.

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Inhibition of hypoxia/reoxygenation-induced oxidative stress in HGF-stimulated antiapoptotic signaling: role of PI3-K and Akt kinase upon rac1

Cited by 106 publications

References 39 publications

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

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

p66Shc has a pivotal function in impaired liver regeneration in aged mice by a redox-dependent mechanism

Alleviation of Aβ-induced cognitive impairment by ultrasound-mediated gene transfer of HGF in a mouse model

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