α-Lipoic acid attenuates LPS-induced cardiac dysfunction through a PI3K/Akt-dependent mechanism

Jiang, Surong; Zhu, Wenwen; Li, Chuanfu; Zhang, Xiaojin; Lu, Ting; Ding, Zhengnian; Cao, Kejiang; Liu, Li

doi:10.1016/j.intimp.2013.03.024

Cited by 51 publications

(42 citation statements)

References 37 publications

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“…42) Akt seemed to be one of the key points to link inflammation, autophagy, and apoptosis. In consistence with previous reports, 39,40) we found that the phosphorylation level of Akt was decreased 4 h after LPS injection. This result may explain the increase of autophagic activity after LPS injection that LPS induced autophagy through inhibition of Akt/mTOR pathway, as reported by previous studies.…”

Section: Discussionsupporting

confidence: 92%

“…During the early stage (less than 6 h), LPS administration decrease the phosphorylation of Akt. [39][40][41] It had been demonstrated that, activation of Akt/mTOR pathway leads to inhibition of autophagy. 30,31) Moreover, studies on glioma cells showed that induction of apoptosis required the triple Notes: Top left: Typical autophagosome (AP, arrow head) with double membrane containing intact mitochondria and autolysosomes (AL, asterisks) with electron-dense amorphous material prevailing in cardiomyocytes of mice from TO + LPS group.…”

Section: Discussionmentioning

confidence: 99%

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Liver X receptor activation protects against inflammation and enhances autophagy in myocardium of neonatal mouse challenged by lipopolysaccharides

Liu

Gao

et al. 2014

Bioscience, Biotechnology, and Biochemistry

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Liver X receptors (LXRs) has been emerged as negative regulators of cardiomyocytic inflammation. The cellular process of autophagy is believed to play a protective role in myocardium during the inflammatory status. In this study, we investigated the role of LXRs agonist TO901317 (TO) on lipopolysaccharides (LPS)-induced myocardial inflammation and autophagy. The results showed that TO pretreatment significantly reduced the LPS-induced infiltration of inflammatory cells, elevation of NF-κB protein, TNF-α, and IL-6 mRNA levels in the myocardium. Moreover, LPS stimulated autophagy in neonatal mice heart, and this effect was further enhanced by TO pretreatment as evidenced by increased LC3-II/ GAPDH ratio increment. Furthermore, TUNEL assay revealed LPS stimulation also increased the number of apoptotic cells in the myocardium, and the increment was inhibited by TO pretreatment. Our findings suggested that attenuation of inflammation and apoptosis, and enhancement of autophagy by TO may contribute to the protection of myocardium under inflammatory condition.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Liver X receptor activation protects against inflammation and enhances autophagy in myocardium of neonatal mouse challenged by lipopolysaccharides

Liu

Gao

et al. 2014

Bioscience, Biotechnology, and Biochemistry

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“…The PI3K signaling pathway has been implicated in inflammation and sepsis. Studies have shown that PI3K signaling plays a protective role in sepsis and that inhibition of PI3K signaling increases mortality in experimental sepsis [134,135,136]. However, it must be stressed that most of these studies used pharmacological agents that globally inhibit PI3K signaling.…”

Section: The Role Of Pi3ksmentioning

confidence: 99%

In Search of a Cure for Sepsis: Taming the Monster in Critical Care Medicine

Okeke

Uzonna²

2016

J Innate Immun

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In spite of over half a century of research, sepsis still constitutes a major problem in health care delivery. Although advances in research have significantly increased our knowledge of the pathogenesis of sepsis and resulted in better prognosis and improved survival outcome, sepsis still remains a major challenge in modern medicine with an increase in occurrence predicted and a huge socioeconomic burden. It is generally accepted that sepsis is due to an initial hyperinflammatory response. However, numerous efforts aimed at targeting the proinflammatory cytokine network have been largely unsuccessful and the search for novel potential therapeutic targets continues. Recent studies provide compelling evidence that dysregulated anti-inflammatory responses may also contribute to sepsis mortality. Our previous studies on the role of regulatory T cells and phosphoinositide 3-kinases in sepsis highlight immunological approaches that could be explored for sepsis therapy. In this article, we review the current and emerging concepts in sepsis, highlight novel potential therapeutic targets and immunological approaches for sepsis treatment and propose a biphasic treatment approach for management of the condition.

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“…LA has been found to prevent hydrogen peroxide-induced neuron damage (Zhang et al 2001) , protect neurons from neurotoxicity , and reduce oxidative damage following stroke through enhancing endogenous antioxidant level (Hall et al 2010;Bilska and Wlodek 2005;Connell et al 2011). In addition, LA has also capacity to inhibit LPS-induced inflammatory process (Zhang et al 2007;Suh et al 2014;Jiang et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Lipoic acid protects dopaminergic neurons in LPS-induced Parkinson’s disease model

et al. 2015

Metab Brain Dis

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Parkinson's disease (PD) is a chronic neurodegenerative disease of the central nervous system (CNS), characterized by a loss of dopaminergic neurons, which is thought to be caused by both genetic and environmental factors. Recent findings suggest that neuroinflammation may be a pathogenic factor in the onset and progression of sporadic PD. Here we explore the potential therapeutic effect of lipoic acid (LA) on a lipolysaccharide (LPS)-induced inflammatory PD model. Our results for the first time showed that LA administration improved motor dysfunction, protected dopaminergic neurons loss, and decreased α-synuclein accumulation in the substantia nigra (SN) area of brain. Further, LA inhibited the activation of nuclear factor-κB (NF-κB) and expression of pro-inflammatory molecules in M1 microglia. Taken together, these results suggest that LA may exert a profound neuroprotective effect and is thus a promising anti-neuroinflammatory and anti-oxidative agent for halting the progression of PD. Interventions aimed at either blocking microglia-derived inflammatory mediators or modulating the polarization of microglia may be potentially useful therapies that are worth further investigation.

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α-Lipoic acid attenuates LPS-induced cardiac dysfunction through a PI3K/Akt-dependent mechanism

Cited by 51 publications

References 37 publications

Liver X receptor activation protects against inflammation and enhances autophagy in myocardium of neonatal mouse challenged by lipopolysaccharides

Liver X receptor activation protects against inflammation and enhances autophagy in myocardium of neonatal mouse challenged by lipopolysaccharides

In Search of a Cure for Sepsis: Taming the Monster in Critical Care Medicine

Lipoic acid protects dopaminergic neurons in LPS-induced Parkinson’s disease model

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