Spermidine‐enhanced autophagic flux improves cardiac dysfunction following myocardial infarction by targeting the AMPK/mTOR signalling pathway

Yan, Jing; Wang, Yuxi; Ling, Yuanna; Song, Xudong; Wang, Si-Yi; Liu, Haiqiong; Liu, Qicai; Zhang, Ya; Yang, Pingzhen; Wang, Xianbao; Chen, Aihua

doi:10.1111/bph.14706

Cited by 66 publications

(49 citation statements)

References 56 publications

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“…180 Similarly, luteolin was found to enhance autophagic flux, improve mitochondria function, and inhibit apoptosis through Mst1 inhibition. 181 Aside from trehalose, melatonin, and luteolin, restoration of autophagic flux was also induced by nobiletin 182 and spermidine 183 in animal models of MI or MI-induced heart failure, and most of them exert protection against MI via activating autophagy or accelerating autophagy flux. [179][180][181][182][183]…”

Section: Natural Products In Preventing MImentioning

confidence: 99%

Autophagy and cardiac diseases: Therapeutic potential of natural products

Liu

et al. 2020

Medicinal Research Reviews

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The global incidence of cardiac diseases is expected to increase in the coming years, imposing a substantial socioeconomic burden on healthcare systems. Autophagy is a tightly regulated lysosomal degradation mechanism important for cell survival, homeostasis, and function. Accumulating pieces of evidence have indicated a major role of autophagy in the regulation of cardiac homeostasis and function. It is well established that dysregulation of autophagy in cardiomyocytes is involved in cardiac hypertrophy, myocardial infarction, diabetic cardiomyopathy, and heart failure. In this sense, autophagy seems to be an attractive therapeutic target for cardiac diseases. Recently, multiple natural products/phytochemicals, such as resveratrol, berberine, and curcumin have been shown to regulate cardiomyocyte autophagy via different pathways. The autophagy‐modifying capacity of these compounds should be taken into consideration for designing novel therapeutic agents. This review focuses on the role of autophagy in various cardiac diseases and the pharmacological basis and therapeutic potential of reported natural products in cardiac diseases by modifying autophagic processes.

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Section: Natural Products In Preventing MImentioning

confidence: 99%

Autophagy and cardiac diseases: Therapeutic potential of natural products

Liu

et al. 2020

Medicinal Research Reviews

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“…Recently, it has been reported that autophagy inhibition or autophagy flux impairment can cause cardiac hypertrophy [3][4][5][6]. Enhanced autophagy may attenuate cardiac hypertrophy [7][8][9]. In bronchial epithelial cells, nicotine was reported to be involved in the regulation of autophagy and emphysema progression [10,11].…”

Section: Ivyspringmentioning

confidence: 99%

Cilostazol alleviate nicotine induced cardiomyocytes hypertrophy through modulation of autophagy by CTSB/ROS/p38MAPK/JNK feedback loop

Wang¹,

Xi²,

Hu³

et al. 2020

Int. J. Biol. Sci.

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Nicotine is proved to be an important factor for cardiac hypertrophy. Autophagy is important cell recycling system involved in the regulation of cardiac hypertrophy. Cilostazol, which is often used in the management of peripheral vascular disease. However, the effects of cilostazol on nicotine induced autophagy and cardiac hypertrophy are unclear. Here, we aim to determine the role and molecular mechanism of cilostazol in alleviating nicotine-induced cardiomyocytes hypertrophy through modulating autophagy and the underlying mechanisms. Our results clarified that nicotine stimulation caused cardiomyocytes hypertrophy and autophagy flux impairment significantly in neonatal rat ventricular myocytes (NRVMs), which were evidenced by augments of LC3-II and p62 levels, and impaired autophagosomes clearance. Interestingly, cathepsin B (CTSB) activity decreased dramatically after stimulation with nicotine in NRVMs, which was crucial for substrate degradation in the late stage of autophagy process, and cilostazol could reverse this effect dramatically. Intracellular ROS levels were increased significantly after nicotine exposure. Meanwhile, p38MAPK and JNK were activated after nicotine treatment. By using ROS scavenger N-acetyl-cysteine (NAC) could reverse the effects of nicotine by down-regulation the phosphorylation of p38MAPK and JNK pathways, and pretreatment of specific inhibitors of p38MAPK and JNK could restore the autophagy impairment and cardiomyocytes hypertrophy induced by nicotine. Moreover, CTSB activity of lysosome regained after the treatment with cilostazol. Cilostazol also inhibited the ROS accumulation and the activation of p38MAPK and JNK, which providing novel connection between lysosome CTSB and ROS/p38MAPK/JNK related oxidative stress pathway. This is the first demonstration that cilostazol could alleviate nicotine induced cardiomyocytes hypertrophy through restoration of autophagy flux by activation of CTSB and inhibiting ROS/p38/JNK pathway, exhibiting a feedback loop on regulation of autophagy and cardiomyocytes hypertrophy.

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“…Recent reports have pointed at the ability of SPD to counteract disc degeneration via enhancement of autophagy in the cells of the nucleus pulposus [9] as well as its ability to reduce oxidative damage and inflammation in a model of cardiac infarction via enhancing the AMPK/ mTOR-mediated autophagic flux [10].…”

Section: Introductionmentioning

confidence: 99%

Spermidine rescues the deregulated autophagic response to oxidative stress of osteoarthritic chondrocytes

D’Adamo

Cetrullo

Guidotti

et al. 2020

Free Radical Biology and Medicine

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Oxidative stress (OS) contributes to Osteoarthritis (OA) pathogenesis and its effects are worsened by the impairment of homeostatic mechanisms such as autophagy in OA chondrocytes. Rescue of an efficient autophagic flux could therefore reduce the bulk of damaged molecules, and at the same time improve cell function and viability. As a promising dietary or intra-articular supplement to rescue autophagy in OA chondrocytes, we tested spermidine (SPD), known to induce autophagy and to reduce OS in several other cellular models. Chondrocytes were obtained from OA cartilage and seeded at high-density to keep their differentiated phenotype. The damaging effects of OS and the chondroprotective activity of SPD were assessed by evaluating the extent of cell death, oxidative DNA damage and caspase 3 activation. The autophagy promoting activity of SPD was evaluated by assessing pivotal autophagic effectors, i.e. Beclin-1 (BECN-1), microtubule-associated protein 1 light chain 3 II (LC3-II) and p62. BECN-1 protein expression was significantly increased by SPD and reduced by H 2 O 2 treatment. SPD also rescued the impaired autophagic flux consequent to H 2 O 2 exposure by increasing mRNA and protein expression of LC3-II and p62. SPD induction of mitophagy was revealed by immunofluorescent co-localization of LC3-II and TOM20. The key protective role of autophagy was confirmed by the loss of SPD chondroprotection upon autophagy-related gene 5 (ATG5) silencing. Significant SPD tuning of the H 2 O 2-dependent induction of degradative (MMP-13) inflammatory (iNOS, COX-2) and hypertrophy markers (RUNX2 and VEGF) was revealed by Real Time PCR and pointed at the SPD ability of reducing NF-κB activation through autophagy induction. Conversely, blockage of autophagy led to parallel increases of oxidative markers and p65 nuclear translocation. SPD also increased the proliferation of slow-proliferating primary cultures.Taken together, our findings highlight the chondroprotective, anti-oxidant and anti-inflammatory activity of SPD and suggest that the protection afforded by SPD against OS is exerted through the rescue of the autophagic flux.

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Spermidine‐enhanced autophagic flux improves cardiac dysfunction following myocardial infarction by targeting the AMPK/mTOR signalling pathway

Cited by 66 publications

References 56 publications

Autophagy and cardiac diseases: Therapeutic potential of natural products

Autophagy and cardiac diseases: Therapeutic potential of natural products

Cilostazol alleviate nicotine induced cardiomyocytes hypertrophy through modulation of autophagy by CTSB/ROS/p38MAPK/JNK feedback loop

Spermidine rescues the deregulated autophagic response to oxidative stress of osteoarthritic chondrocytes

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