Cilostazol protects against myocardial ischemia and reperfusion injury by activating transcription factor EB (TFEB)

Li, Jiangjin; Xiang, Xiaoli; Xu, Zhigang

doi:10.1002/bab.1754

Cited by 18 publications

(11 citation statements)

References 41 publications

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“…For example, sustain-releasing H 2 S donor 5-(4-methoxyphenyl)-3H-1, 2-dithiole-3-thione [ 155 ], metformin [ 271 ], and sevoflurane precondition [ 272 ] restore the impaired autophagic flux induced by MI/RI through AMPK activation, thus protecting the myocardium from MI/RI. Intermittent fasting [ 273 ] and cilostazol [ 274 ] protect against myocardial ischemia/reperfusion injury by transcription factor EB-mediated transcriptional initiation of autophagy-lysosome mechanisms. Transient hypoxia can also protect against reperfusion injury by slightly upregulating autophagy [ 275 ].…”

Section: Interventions Targeting Oxidative Stress and Related Pathways In Myocardial Reperfusionmentioning

confidence: 99%

Role of Oxidative Stress in Reperfusion following Myocardial Ischemia and Its Treatments

Xiang

Xin

et al. 2021

Oxidative Medicine and Cellular Longevity

161

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Myocardial ischemia is a disease with high morbidity and mortality, for which reperfusion is currently the standard intervention. However, the reperfusion may lead to further myocardial damage, known as myocardial ischemia/reperfusion injury (MI/RI). Oxidative stress is one of the most important pathological mechanisms in reperfusion injury, which causes apoptosis, autophagy, inflammation, and some other damage in cardiomyocytes through multiple pathways, thus causing irreversible cardiomyocyte damage and cardiac dysfunction. This article reviews the pathological mechanisms of oxidative stress involved in reperfusion injury and the interventions for different pathways and targets, so as to form systematic treatments for oxidative stress-induced myocardial reperfusion injury and make up for the lack of monotherapy.

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Section: Interventions Targeting Oxidative Stress and Related Pathways In Myocardial Reperfusionmentioning

confidence: 99%

Role of Oxidative Stress in Reperfusion following Myocardial Ischemia and Its Treatments

Xiang

Xin

et al. 2021

Oxidative Medicine and Cellular Longevity

161

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“…In myocardial ischemia and reperfusion injury, cardiomyocyte death can be caused by lysosomal consumption, which manifests as a decrease in the number of lysosomes and the downregulated expression of LAMP-1 139 . Both the enhancement of lysosomal function and promotion of autophagy were reportedly beneficial by alleviating cardiomyocyte death after myocardial ischemia and reperfusion injury 139,143 . In proteotoxic cardiomyopathy, cardiomyocytes showed impaired autophagic flux and reduced lysosome abundance; however, adeno-associated virus-TFEB transduction was sufficient to reverse cardiomyopathy pathology in a preclinical study 142 .…”

Section: Cardiovascular Diseasesmentioning

confidence: 99%

Lysosomal quality control of cell fate: a novel therapeutic target for human diseases

Zhu

Yao

et al. 2020

Cell Death Dis

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In eukaryotic cells, lysosomes are digestive centers where biological macromolecules are degraded by phagocytosis and autophagy, thereby maintaining cellular self-renewal capacity and energy supply. Lysosomes also serve as signaling hubs to monitor the intracellular levels of nutrients and energy by acting as platforms for the assembly of multiple signaling pathways, such as mammalian target of rapamycin complex 1 (mTORC1) and adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK). The structural integrity and functional balance of lysosomes are essential for cell function and viability. In fact, lysosomal damage not only disrupts intracellular clearance but also results in the leakage of multiple contents, which pose great threats to the cell by triggering cell death pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis. The collapse of lysosomal homeostasis is reportedly critical for the pathogenesis and development of various diseases, such as tumors, neurodegenerative diseases, cardiovascular diseases, and inflammatory diseases. Lysosomal quality control (LQC), comprising lysosomal repair, lysophagy, and lysosomal regeneration, is rapidly initiated in response to lysosomal damage to maintain lysosomal structural integrity and functional homeostasis. LQC may be a novel but pivotal target for disease treatment because of its indispensable role in maintaining intracellular homeostasis and cell fate.

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“…Cilostazol, as a selective inhibitor of phosphodiesterase-3, has been known for increasing intracellular cAMP levels [12,13]. While Bai Y et.al reported that cilostazol can attenuate superoxide production and reduce the infarct size in rabbit by activating CTSB [14].…”

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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Cilostazol protects against myocardial ischemia and reperfusion injury by activating transcription factor EB (TFEB)

Cited by 18 publications

References 41 publications

Role of Oxidative Stress in Reperfusion following Myocardial Ischemia and Its Treatments

Role of Oxidative Stress in Reperfusion following Myocardial Ischemia and Its Treatments

Lysosomal quality control of cell fate: a novel therapeutic target for human diseases

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

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