Efficacy of sauchinone as a novel AMPK-activating lignan for preventing iron-induced oxidative stress and liver injury

Kim, Young Woo; Lee, Sung Min; Shin, Sook; Hwang, Se Jin; Brooks, Janie S.; Kang, Hee Eun; Lee, Myung Gull; Kim, Sang Chan; Kim, Sang Geon

doi:10.1016/j.freeradbiomed.2009.07.018

Cited by 98 publications

(72 citation statements)

References 40 publications

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“…Moreover, the production of proinflammatory mediators including AA is increased under ironoverload conditions (Galaris and Pantopoulos, 2008). Indeed, we found an increase in plasma AA levels after iron deposition in an in vivo model, in which phenylhydrazine was used as a hemolytic agent that indirectly creates hepatic iron overload and promotes oxidative damage (Ferrali et al, 1997;Kim et al, 2009). AA treatment alone promotes ROS production, causes MMP changes, and thereby leads to cell death (Kwon et al, 2009).…”

Section: Discussionmentioning

confidence: 83%

Resveratrol Protects Mitochondria against Oxidative Stress through AMP-Activated Protein Kinase-Mediated Glycogen Synthase Kinase-3β Inhibition Downstream of Poly(ADP-ribose)polymerase-LKB1 Pathway

Shin¹,

Cho²,

Kim³

2009

Mol Pharmacol

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189

136

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Arachidonic acid (AA, a proinflammatory fatty acid) in combination with iron promotes excess reactive oxygen species (ROS) production and exerts a deleterious effect on mitochondria. We have shown previously that activation of AMP-activated protein kinase (AMPK) protects hepatocytes from AA ϩ iron-induced apoptosis. Resveratrol, a polyphenol in grapes, has beneficial effects mediated through SIRT1, LKB1, and AMPK. This study investigated the potential of resveratrol to protect against the mitochondrial impairment induced by AA ϩ iron and the underlying mechanism for this cytoprotection. Resveratrol treatment inhibited apoptosis, ROS production, and glutathione depletion elicited by AA ϩ iron in HepG2 cells. In addition, resveratrol attenuated superoxide generation in mitochondria and inhibited mitochondrial dysfunction induced by AA ϩ iron. Overall, AMPK activation by resveratrol contributed to cell survival, as supported by the reversal of its restoration of mitochondrial membrane potential by either overexpression of a dominant-negative mutant of AMPK␣ or compound C treatment. Resveratrol increased inhibitory phosphorylation of glycogen synthase kinase-3␤ (GSK3␤) downstream of AMPK, which contributed to mitochondrial protection and cell survival. Likewise, small interfering RNA knockdown of LKB1, an upstream kinase of AMPK, reduced the ability of resveratrol to protect cells from mitochondrial dysfunction. Furthermore, this LKB1-dependent mitochondrial protection resulted from resveratrol's poly(ADP-ribose)polymerase activation, but not SIRT1 activation, as supported by the experiment using 3-aminobenzamide, a poly(ADP-ribose)polymerase inhibitor. Other polyphenols, such as apigenin, genistein, and daidzein, did not activate AMPK or protect mitochondria against AA ϩ iron. Thus, resveratrol protects cells from AA ϩ iron-induced ROS production and mitochondrial dysfunction through AMPKmediated inhibitory phosphorylation of GSK3␤ downstream of poly(ADP-ribose)polymerase-LKB1 pathway.

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Section: Discussionmentioning

confidence: 83%

Resveratrol Protects Mitochondria against Oxidative Stress through AMP-Activated Protein Kinase-Mediated Glycogen Synthase Kinase-3β Inhibition Downstream of Poly(ADP-ribose)polymerase-LKB1 Pathway

Shin¹,

Cho²,

Kim³

2009

Mol Pharmacol

Self Cite

189

136

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“…It has been reported that AMPK inhibitor compound C could lead to ceramide accumulation and apoptotic cell death in MCF-7 breast carcinoma cells [6]. Moreover, several recent reports showed that AMPK activation showed anti-apoptotic effects in different cell types [20][21][22]. All these studies suggested the possibility that AMPK inhibition could play a pro-apoptotic role as well as a novel TRAIL sensitizer in cancer cells.…”

Section: Discussionmentioning

confidence: 95%

Compound C sensitizes Caki renal cancer cells to TRAIL-induced apoptosis through reactive oxygen species-mediated down-regulation of c-FLIPL and Mcl-1

Jang

Lee

Yang

et al. 2010

Experimental Cell Research

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“…Although AMPK signaling is intricately tied to energy metabolism and homeostasis, it is also critical for various physiological processes including inflammation, and proliferation [60,61] . It is noteworthy that the AMPKassociated pathway may suppress apoptosis induced by glucocorticoids [62] , hyperglycemia [63] , hepatic ischemiareperfusion [64] and oxidative stress [65][66][67][68][69] . AMPK activation has a beneficial effect on cell viability via protection of mitochondria from apoptosis: phosphorylation of glycogen synthase kinase 3β (GSK3β) [66] , and phosphorylation of Bad, which leads to inhibition of cytochrome c release and attenuation of caspase-3 activity [70] .…”

Section: Cytoprotective Effect Of Ampkmentioning

confidence: 99%

“…AMPK activation has a beneficial effect on cell viability via protection of mitochondria from apoptosis: phosphorylation of glycogen synthase kinase 3β (GSK3β) [66] , and phosphorylation of Bad, which leads to inhibition of cytochrome c release and attenuation of caspase-3 activity [70] . AMPK is also implicated in other pathophysiological responses in various cell types: a decrease in endoplasmic reticulum (ER) stress [71] , DNA damage repair [72,73] , autophagy [74,75] , and the antioxidant defense system [65][66][67][68][69] . This review focuses on the role of AMPK in hepatocyte viability.…”

Section: Cytoprotective Effect Of Ampkmentioning

confidence: 99%

AMPK-associated signaling to bridge the gap between fuel metabolism and hepatocyte viability

Yang¹,

Han²,

Kim

et al. 2010

WJG

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The adenosine monophosphate-activated protein kinase (AMPK) and p70 ribosomal S6 kinase-1 pathway may serve as a key signaling flow that regulates energy metabolism; thus, this pathway becomes an attractive target for the treatment of liver diseases that result from metabolic derangements. In addition, AMPK emerges as a kinase that controls the redox-state and mitochondrial function, whose activity may be modulated by antioxidants. A close link exists between fuel metabolism and mitochondrial biogenesis. The relationship between fuel metabolism and cell survival strongly implies the existence of a shared signaling network, by which hepatocytes respond to challenges of external stimuli. The AMPK pathway may belong to this network. A series of drugs and therapeutic candidates enable hepatocytes to protect mitochondria from radical stress and increase cell viability, which may be associated with the activation of AMPK, liver kinase B1, and other molecules or components. Consequently, the components downstream of AMPK may contribute to stabilizing mitochondrial membrane potential for hepatocyte survival. In this review, we discuss the role of the AMPK pathway in hepatic energy metabolism and hepatocyte viability. This information may help identify ways to prevent and/or treat hepatic diseases caused by the metabolic syndrome. Moreover, clinical drugs and experimental therapeutic candidates that directly or indirectly modulate the AMPK pathway in distinct manners are discussed here with particular emphasis on their effects on fuel metabolism and mitochondrial function.

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Efficacy of sauchinone as a novel AMPK-activating lignan for preventing iron-induced oxidative stress and liver injury

Cited by 98 publications

References 40 publications

Resveratrol Protects Mitochondria against Oxidative Stress through AMP-Activated Protein Kinase-Mediated Glycogen Synthase Kinase-3β Inhibition Downstream of Poly(ADP-ribose)polymerase-LKB1 Pathway

Resveratrol Protects Mitochondria against Oxidative Stress through AMP-Activated Protein Kinase-Mediated Glycogen Synthase Kinase-3β Inhibition Downstream of Poly(ADP-ribose)polymerase-LKB1 Pathway

Compound C sensitizes Caki renal cancer cells to TRAIL-induced apoptosis through reactive oxygen species-mediated down-regulation of c-FLIPL and Mcl-1

AMPK-associated signaling to bridge the gap between fuel metabolism and hepatocyte viability

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