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The endotoxemia cardiac dysfunction is attenuated by AMPK/mTOR signaling pathway regulating autophagy.

Published on Oct 1, 2017in Biochemical and Biophysical Research Communications2.71
· DOI :10.1016/j.bbrc.2017.08.034
Jie Zhang1
Estimated H-index: 1
(UMMC: University of Mississippi Medical Center),
Peng Zhao1
Estimated H-index: 1
(SDU: Shandong University)
+ 5 AuthorsJi Li6
Estimated H-index: 6
(UMMC: University of Mississippi Medical Center)
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Abstract
Abstract AMP-activated protein kinase (AMPK), an enzyme that plays a role in cellular energy homeostasis, modulates myocardial signaling in the heart. Myocardial dysfunction is a common complication of sepsis. Autophagy is involved in the aging related cardiac dysfunction. However, the role of AMPK in sepsis-induced cardiotoxicity has yet to be clarified, especially in aging. In this study, we explored the role of AMPK in lipopolysaccharide (LPS)-induced myocardial dysfunction and elucidated the potential mechanisms of AMPK/mTOR pathway regulating autophagy in young and aged mice. We harvested cardiac tissues by intraperitoneal injection of LPS treatment. The results by echocardiography, pathology, contractile and intracellular Ca 2+ property as well as western blot analysis revealed that LPS induced remarkable cardiac dysfunction and cardiotoxicity in mice hearts and cardiomyocytes, which were more seriously in the aged mice. Western blot analysis indicated that the underlying mechanisms included inhibition autophagy mediated by AMPK/mTOR activation. LPS overtly promoted the expression of AMPK upstream regulator PP2A and PP2Cα. Pharmacological activation of AMPK improved cardiac function and upregulated cardiac autophagy induced by LPS in the aged mice. Collectively, our findings suggest that upregulation of autophagy by administration of AMPK could attenuate LPS-induced cardiotoxicity, which enhances our knowledge to explore new drugs and strategies for combating cardiac dysfunction induced by sepsis.
  • References (27)
  • Citations (7)
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References27
Newest
Published on Aug 1, 2017in Biochimica et Biophysica Acta3.79
Yanyan Ma1
Estimated H-index: 1
(Fourth Military Medical University),
Lifang Yang10
Estimated H-index: 10
(Fourth Military Medical University)
+ 4 AuthorsJian Yang14
Estimated H-index: 14
(Fourth Military Medical University)
Abstract Doxorubicin as anticancer agent can cause dose-dependent cardiotoxicity and heart failure in the long term. Rutin as a polyphenolic flavonoid has been illustrated to protect hearts from diverse cardiovascular diseases. Its function is known to be related to its antioxidant and antiinflammatory activity which may regulate multiple cellular signal pathways. However, the role of rutin on doxorubicin-induced cardiotoxicity has yet to be discovered. In this study, we explored the protective ...
Published on Jul 1, 2017in Apoptosis4.02
Tao Pu1
Estimated H-index: 1
(CQMU: Chongqing Medical University),
Xiao-hui Liao5
Estimated H-index: 5
(CQMU: Chongqing Medical University)
+ 5 AuthorsQi Liu5
Estimated H-index: 5
(CQMU: Chongqing Medical University)
Autophagy may have protective effects in renal ischemia–reperfusion (I/R) injury, although the underlying mechanisms remain unclear. Augmenter of liver regeneration (ALR), a widely distributed multifunctional protein that is originally identified as a hepatic growth factor, may participate in the process of autophagy. To investigate the role of ALR in autophagy, ALR expression is knocked-down in human kidney 2 (HK-2) cells with short hairpin RNA lentivirals. Then, the level of autophagy is measu...
Published on Apr 4, 2017in Frontiers in Pharmacology3.85
Hsing-Hui Su2
Estimated H-index: 2
(NYMU: National Yang-Ming University),
Ya-Chun Chu1
Estimated H-index: 1
(Taipei Veterans General Hospital)
+ 7 AuthorsShiang-Suo Huang14
Estimated H-index: 14
(CSMU: Chung Shan Medical University)
The incidence of myocardial ischemia-reperfusion (IR) injury is rapidly increasing around the world and this disease is a major contributor to global morbidity and mortality. It is known that regulation of programmed cell death including apoptosis and autophagy reduces the impact of myocardial IR injury. In this study, the cardioprotective effects and underlying mechanisms of Phellinus linteus (Berk. & Curt.) Teng, Hymenochaetaceae (PL), a type of medicinal mushroom, were examined in rats subjec...
Gustavo Ramos3
Estimated H-index: 3
,
Anne van den Berg1
Estimated H-index: 1
+ 13 AuthorsKatrin G. Heinze8
Estimated H-index: 8
(University of Würzburg)
In recent years, the myocardium has been rediscovered under the lenses of immunology, and lymphocytes have been implicated in the pathogenesis of cardiomyopathies with different etiologies. Aging is an important risk factor for heart diseases, and it also has impact on the immune system. Thus, we sought to determine whether immunological activity would influence myocardial structure and function in elderly mice. Morphological, functional, and molecular analyses revealed that the age-related myoc...
Published on Feb 27, 2017in The EMBO Journal11.23
Manuela Barilari1
Estimated H-index: 1
(French Institute of Health and Medical Research),
Gregory Bonfils1
Estimated H-index: 1
(French Institute of Health and Medical Research)
+ 4 AuthorsMario Pende34
Estimated H-index: 34
(French Institute of Health and Medical Research)
The inactivation of S6 kinases mimics several aspects of caloric restriction, including small body size, increased insulin sensitivity and longevity. However, the impact of S6 kinase activity on cellular senescence remains to be established. Here, we show that the constitutive activation of mammalian target of rapamycin complex 1 (mTORC1) by tuberous sclerosis complex (TSC) mutations induces a premature senescence programme in fibroblasts that relies on S6 kinases. To determine novel molecular t...
Published on Oct 1, 2016in Biochemical and Biophysical Research Communications2.71
Michelle S. Go5
Estimated H-index: 5
(UIC: University of Illinois at Chicago),
Jinghong Kou8
Estimated H-index: 8
(UIC: University of Illinois at Chicago)
+ 2 AuthorsKen-ichiro Fukuchi7
Estimated H-index: 7
(UIC: University of Illinois at Chicago)
Abstract Microglia-mediated clearance of amyloid beta-protein (Aβ) via Toll-like receptor 4 (TLR4) signaling may play an important role in the pathogenesis of Alzheimer's disease (AD). However, as the disease progresses, activated microglia appear to become incapable of clearing Aβ deposits. Because repeated exposure to a TLR4 ligand leads to a diminished response of monocytes/macrophages to lipopolysaccharide (LPS) and because aggregated Aβ is a TLR4 ligand, we hypothesize that chronic exposure...
Gadi Lalazar14
Estimated H-index: 14
(Albert Einstein College of Medicine),
Ghulam Ilyas3
Estimated H-index: 3
(Albert Einstein College of Medicine)
+ 6 AuthorsMark J. Czaja5
Estimated H-index: 5
(Albert Einstein College of Medicine)
Autophagy is required for hepatocytes to resist injury from high concentrations of LPS. With a genetic decrease in hepatocyte autophagy, increased liver injury occurred in response to LPS from sensitization to TNF-dependent hepatocellular death in association with an impairment in Akt signaling. Human conditions such as aging and hepatic steatosis may worsen the clinical outcome from sepsis as the result of their concomitant decrease in hepatic levels of autophagy.
Published on Aug 2, 2016in Autophagy11.06
Min-Ji Kim13
Estimated H-index: 13
(Yonsei University),
Soo Han Bae9
Estimated H-index: 9
(Yonsei University)
+ 15 AuthorsMin Goo Lee48
Estimated H-index: 48
(Yonsei University)
ABSTRACTProper regulation of mitophagy for mitochondrial homeostasis is important in various inflammatory diseases. However, the precise mechanisms by which mitophagy is activated to regulate inflammatory responses remain largely unknown. The NLRP3 (NLR family, pyrin domain containing 3) inflammasome serves as a platform that triggers the activation of CASP1 (caspase 1) and secretion of proinflammatory cytokines. Here, we demonstrate that SESN2 (sestrin 2), known as stress-inducible protein, sup...
Published on May 1, 2016in Toxicological Sciences3.56
Wanqing Sun5
Estimated H-index: 5
(UMMC: University of Mississippi Medical Center),
Nanhu Quan5
Estimated H-index: 5
(UMMC: University of Mississippi Medical Center)
+ 6 AuthorsJi Li6
Estimated H-index: 6
(UMMC: University of Mississippi Medical Center)
Published on Apr 1, 2016in Biogerontology3.81
Mirjana Dimitrijević16
Estimated H-index: 16
(University of Belgrade),
Stanislava Stanojević13
Estimated H-index: 13
+ 6 AuthorsGordana Leposavić16
Estimated H-index: 16
(University of Belgrade)
Macrophages undergo significant functional alterations during aging. The aim of the present study was to investigate changes of rat macrophage functions and response to M1/M2 polarization signals with age. Therefore, resident and thioglycollate-elicited peritoneal macrophages from young (3-month-old) and aged (18–19-month-old) rats were tested for phagocytic capacity and ability to secrete inflammatory mediators following in vitro stimulation with LPS and GM-CSF, and IL-4, prototypic stimulators...
Cited By7
Newest
Published on 2019in Frontiers in Physiology3.20
Yin Xin (GU: Guangzhou University), Huang Xin (GU: Guangzhou University)+ 2 AuthorsGuo Liheng (GU: Guangzhou University)
Sepsis is a systemic inflammatory disease with infection, and autophagy has been shown to play an important role in sepsis. This review summarizes the main regulatory mechanisms of autophagy in sepsis and its latest research. Recent studies have shown that autophagy can regulate innate immune processes and acquired immune processes, and the regulation of autophagy in different immune cells is different. Mitochondrial autophagy can select damaged mitochondria and remove it to deal with oxidative ...
Published on Apr 1, 2019in Canadian Journal of Cardiology5.59
Wei Cheng1
Estimated H-index: 1
(Peking Union Medical College Hospital),
Wei Cheng Mm (Peking Union Medical College Hospital)+ 3 AuthorsNa Cui5
Estimated H-index: 5
(Peking Union Medical College Hospital)
Abstract Background Sepsis-induced myocardial dysfunction (SIMD) is a life-threatening complication of sepsis. Mammalian target of rapamycin (mTOR) signalling pathway is significantly associated with SIMD in an animal model; however, there have been no clinical studies of the association in humans. Methods We enrolled 88 patients with sepsis who were admitted to the intensive care unit (ICU) between April 2017, and April 2018. Biochemical indexes, hemodynamic parameters, and bedside echocardiogr...
Published on Apr 1, 2019in Inflammation2.94
Hongyang Liu1
Estimated H-index: 1
(Dalian Medical University),
Yan Sun + 4 AuthorsZuowei Pei1
Estimated H-index: 1
(DUT: Dalian University of Technology)
Sepsis is a major health complication causing patient mortality and increased healthcare costs. Cardiac dysfunction, an important consequence of sepsis, affects mortality. We previously reported that thymoquinone (TQ) protected against hyperlipidemia and doxorubicin-induced cardiac damage. This study investigated the possible protective effects of TQ against cardiac damage in septic BALB/c mice. Eight-week-old male BALB/c mice were divided into four groups: control, TQ, cecal ligation and punctu...
Published on Feb 1, 2019in Toxicological Sciences3.56
Xuan Li2
Estimated H-index: 2
(UMMC: University of Mississippi Medical Center),
Jia Liu2
Estimated H-index: 2
(UMMC: University of Mississippi Medical Center)
+ 6 AuthorsJi Li6
Estimated H-index: 6
(UMMC: University of Mississippi Medical Center)
Published on Jan 31, 2019in Bioscience Reports2.54
Xuan Li2
Estimated H-index: 2
(UMMC: University of Mississippi Medical Center),
Jia Liu2
Estimated H-index: 2
(UMMC: University of Mississippi Medical Center)
+ 5 AuthorsJi Li6
Estimated H-index: 6
(UMMC: University of Mississippi Medical Center)
Heart failure (HF) is a serious disease with high mortality. The incidence of this disease has continued to increase over the past decade. All cardiovascular diseases causing dysfunction of various physiological processes can result in HF. AMP-activated protein kinase (AMPK), an energy sensor, has pleiotropic cardioprotective effects and plays a critical role in the progression of HF. In this review, we highlight that AMPK can not only improve the energy supply in the failing heart by promoting ...
Published on Jun 28, 2018in Mediators of Inflammation3.54
Wen Han2
Estimated H-index: 2
(Peking Union Medical College Hospital),
Hao Wang6
Estimated H-index: 6
(Peking Union Medical College Hospital)
+ 3 AuthorsDawei Liu11
Estimated H-index: 11
(Peking Union Medical College Hospital)
Background. Sepsis-induced myocardial dysfunction is a severe clinical problem. Recent studies have indicated that autophagy and myocardial energy depletion play a major role in myocardial dysfunction during sepsis, a mechanistic target of rapamycin (mTOR) as a master sensor of energy status and autophagy mediator; however, there are little data describing its role during sepsis in the heart. Methods. Cecal ligation and puncture (CLP) or sham operation (SHAM) was performed in rats. After treatme...
Published on Feb 1, 2018in Journal of Critical Care2.78
David Bar-Or27
Estimated H-index: 27
,
Matthew M. Carrick13
Estimated H-index: 13
+ 3 AuthorsEdward Brody5
Estimated H-index: 5
Abstract Sepsis is a leading cause of mortality in the U.S. and Europe. Sepsis and septic shock are the results of severe metabolic abnormalities following infection. Aerobic glycolysis (the Warburg Effect) is as much a hallmark of sepsis as it is of cancer. Warburg observed that cancer cells generated energy through glycolysis (generation of ATP through degradation of glucose, usually associated with anaerobic conditions) rather than through oxidative phosphorylation (generation of ATP through ...
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