Adiponectin Relieves Human Adult Cardiac Myocytes Injury Induced by Intermittent Hypoxia

Zhang, Xiaofeng; Rui, Lijun; Lv, Beili; Chen, Fangfang; Cai, Liming

doi:10.12659/msm.912349

Cited by 8 publications

(4 citation statements)

References 36 publications

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“…This result was unexpected considering that AMPK is a critical energy sensor activated by mitochondrial dysfunction, a decrease in ATP concentration and an increase in ADP-AMP/ATP ratio. Consistent with our result, a decrease in AMPK activation has been similarly reported in human adult cardiomyocytes exposed to chronic IH 39 . Inasmuch as the lack of explanation for such inhibition of AMPK by IH, we decided to investigate the effect of metformin, an AMPK activator widely used for efficiently treating type 2 diabetes 40 , that is also a pathology with a high incidence in apneic patients 41 .…”

Section: Discussionsupporting

confidence: 93%

Metformin protects the heart against chronic intermittent hypoxia through AMPK-dependent phosphorylation of HIF-1α

Moulin,

Blachot-Minassian,

Kneppers

et al. 2024

Preprint

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Chronic intermittent hypoxia (IH), a major feature of obstructive sleep apnea syndrome (OSA), is associated with a more severe myocardial infarction. In this study, we performed RNA sequencing of cardiac samples from mice exposed to IH, which reveals a specific transcriptomic signature of the disease, relative to mitochondrial remodeling and cell death. Corresponding to its activation under chronic IH, we stabilized the Hypoxia Inducible Factor-1a (HIF-1a) in cardiac cells in vitro, and observed its association with an increased autophagic flux. In accordance, IH induced autophagy and mitophagy that is decreased in HIF-1a+/_ mice compared to wild-type animals suggesting that HIF-1 plays a significant role in IH-induced mitochondrial remodeling. Next, we showed that the AMPK metabolic sensor, typically activated by mitochondrial stress, is inhibited after 3 weeks of IH in hearts. Therefore, we assessed the effect of metformin, an anti-diabetic drug and potent activator of AMPK, on myocardial response to ischemia-reperfusion (I/R) injury. Daily administration of metformin significantly decreases infarct size without any systemic beneficial effect on insulin-resistance under IH conditions. The cardioprotective effect of metformin is lost in AMPKa2 knock-out mice demonstrating that AMPKa2 isoform promotes metformin-induced cardioprotection in mice exposed to IH. Mechanistically, we found that metformin inhibits IH-induced mitophagy in myocardium and decreases HIF-1a nuclear expression in mice subjected to IH. In vitro demonstrated that metformin induces HIF-1a phosphorylation, decreases its nuclear localization and subsequently HIF-1 transcriptional activity. Collectively, these results identify the AMPKa2 metabolic sensor as a novel modulator of HIF-1 activity. Our data suggest that metformin could be considered as a cardioprotective drug in OSA patients independently of their metabolic status.

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Section: Discussionsupporting

confidence: 93%

Metformin protects the heart against chronic intermittent hypoxia through AMPK-dependent phosphorylation of HIF-1α

Moulin,

Blachot-Minassian,

Kneppers

et al. 2024

Preprint

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“…In addition, the highest MDA concentration reached a maximum of 152 µmol/L after 16 h of treatment. However, possibly because MDA is a subsequent product of ROS generation, the highest values of ROS generation and MDA concentration did not appear at the same time(60, 98). In addition, when living in harsh environments and affected by ROS generation, mitochondria might develop an abnormal state, in which the cell respiratory process is obstructed, and the power plants needed for cell life might have abnormal working conditions(63, 70–72).…”

Section: Discussionmentioning

confidence: 98%

Inhibitory effect ofBacillus subtilisWL-2 and its IturinA lipopeptides againstPhytophthora infestans

Wang

Zhang

et al. 2019

Preprint

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15Potato late blight triggered by Phytophthora infestans ((Mont.) de Bary) represents a 16 great food security threat worldwide and is difficult to control. Currently, Bacillus spp. 17 have been considered biocontrol agents to control many fungal diseases. Here, 18 Bacillus subtilis WL-2 was selected as the antifungal strain with the most potential 19 against P. infestans mycelium growth. Additionally, the functional metabolites 20 extracted from WL-2 were identified as IturinA-family cyclic lipopeptides (CLPs) via 21 2 high-performance liquid chromatography (HPLC) and electrospray ionization mass 22 spectrometry (ESI-MS). Analyses using scanning and transmission electron 23 microscopy (SEM and TEM) revealed that IturinA caused a change in the mycelial 24 surface and damage to the internal cell structure, including cell membrane disruption 25 and irregular organelle formation. Moreover, propidium iodide staining and nucleic 26 acid and protein release were detected to clarify the cell membrane damage caused by 27 IturinA. Additionally, IturinA triggered reactive oxygen species (ROS) generation and 28 malondialdehyde (MDA) production. Mitochondrial membrane potential (MMP), 29 mitochondrial respiratory chain complexes activity (MRCCA), respiratory control rate 30 (RCR), and oxidative phosphorylation efficiency (P/O) assays indicated that P. 31 infestans mitochondria affected by IturinA were so seriously damaged that the MMP 32 and MRCCA declined remarkably and that mitochondrial ATP production ability was 33 weakened. Therefore, IturinA induces cell membrane damage, oxidative stress, and 34 dysfunction of mitochondria, resulting in P. infestans hyphal cell death. As such, the 35 results highlight that B. subtilis WL-2 and IturinA have great potential as candidates for 36 inhibiting P. infestans mycelium growth and controlling potato late blight. 37 IMPORTANCE 38Potato (Solanum tuberosum L.) is the fourth most common global food crop, and 39 its planting area and yield increase yearly. Notably, in 2015, China initiated a potato 40 staple food conversion strategy, and by 2020, approximately 50% of potatoes will 41 be consumed as a staple food. The plant pathogen fungus Phytophthora infestans 42 ((Mont.) de Bary) is the culprit of potato late blight; however, biological agents 43 3 rather than chemicals are highly necessary to control this threatening disease. In 44 this study, we discovered an antifungal substance, IturinA, a lipopeptide produced 45 by Bacillus subtilis WL-2. Moreover, our research revealed the actual mechanism 46 of IturinA against P. infestans mycelium growth and clarified the potential of B. 65Behind rice, wheat, and corn, potato (Solanum tuberosum L.) is the fourth most 66 stable food crop in the world. However, potato production is often endangered by 67 many pathogens. Worryingly, late blight triggered by Phytophthora infestans ((Mont.) 68 de Bary) could directly reduce or even eliminate potato production, and an outbreak 69 of this disease could even result in a grievous ...

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“…Some researches showed that Ang(1-7) supplement significantly increases the levels of adiponectin [28,160], not only in circulation but also in the myocardial [161]. At the same time, more studies in recent years have reported that adiponectin may achieve its protective effect by activating AMPK [162][163][164][165]. Adiponectin or adiponectin receptors agonists activate several downstream signal transduction pathways mediated by AMPK and PPAR-α to improve fibrotic disorders [156].…”

Section: Adiponectinmentioning

confidence: 99%

AMPK: a balancer of the renin–angiotensin system

Liu

et al. 2019

Bioscience Reports

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The renin–angiotensin system (RAS) is undisputedly well-studied as one of the oldest and most critical regulators for arterial blood pressure, fluid volume, as well as renal function. In recent studies, RAS has also been implicated in the development of obesity, diabetes, hyperlipidemia, and other diseases, and also involved in the regulation of several signaling pathways such as proliferation, apoptosis and autophagy, and insulin resistance. AMP-activated protein kinase (AMPK), an essential cellular energy sensor, has also been discovered to be involved in these diseases and cellular pathways. This would imply a connection between the RAS and AMPK. Therefore, this review serves to draw attention to the cross-talk between RAS and AMPK, then summering the most recent literature which highlights AMPK as a point of balance between physiological and pathological functions of the RAS.

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Adiponectin Relieves Human Adult Cardiac Myocytes Injury Induced by Intermittent Hypoxia

Cited by 8 publications

References 36 publications

Metformin protects the heart against chronic intermittent hypoxia through AMPK-dependent phosphorylation of HIF-1α

Metformin protects the heart against chronic intermittent hypoxia through AMPK-dependent phosphorylation of HIF-1α

Inhibitory effect ofBacillus subtilisWL-2 and its IturinA lipopeptides againstPhytophthora infestans

AMPK: a balancer of the renin–angiotensin system

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