IL-20 promotes hypoxia/reoxygenation-induced mitochondrial dysfunction and apoptosis in cardiomyocytes by upregulating oxidative stress by activating the PKC/NADPH oxidase pathway

Tsai, Kun Ling; Hsieh, Pei‐Ling; Chou, Wan Ching; Hung, Ching Hsia; Yang, Hsin Lun; Chang, Yun; Chu, Pei Ming; Chang, Ming Shi; Chan, Shih Hung

doi:10.1016/j.bbadis.2020.165684

Cited by 17 publications

(7 citation statements)

References 30 publications

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“…Importantly, intragastric administration of palmatine notably upregulated the protein level of pAMPK and nuclear Nrf2 in infarcted myocardium of AMI mice, suggesting that the activation of pAMPK/Nrf2 partially participated in the protective effect of palmatine on AMI. Except for the pAMPK/Nrf2 signaling pathway, there were several other pathways that were closely involved in inflammatory response and cardiomyocyte apoptosis during AMI such as the PI3K/AKT signaling pathway (Li et al 2019), PDK-1/AKT signaling pathway (Garikipati et al 2017), NF-κB signaling pathway (Ma et al 2012), and PKC/NADPH oxidase pathway (Tsai et al 2020), and so on. Whether these relevant signaling pathways participated in the protective mechanisms of palmatine on AMI should be explored in the future.…”

Section: Discussionmentioning

confidence: 99%

Palmatine Alleviates Acute Myocardial Infarction Through Activating pAMPK/Nrf2 Signaling Pathway in Mouse Model

Hao

Jiao

2022

Rev. Bras. Farmacogn.

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Acute myocardial infarction is one of the major leading causes for heart failure, which can lead to the irreversible loss of cardiomyocytes and impaired cardiac function. Hence, the efficient therapeutic agents are still urgent. Our study aimed to explore the role of a natural isoquinoline alkaloid, palmatine, in an acute myocardial infarction mouse model. In this study, intragastric administrated palmatine significantly enhanced left ventricle ejection fraction and left ventricle end-systolic of infarcted mice heart. Meanwhile, palmatine administration partially recovered myocardial structure and attenuated the cardiac fibrosis and infiltration of inflammatory cells. In addition, the usage of palmatine further enhanced the increased transforming growth factor (TGF)-beta1 level, reduced the elevated tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta level in the myocardium of acute myocardial infarction–induced mice, as well as elevated the reduced superoxide dismutase production and inhibited the increased malondialdehyde secretion in infarcted myocardium of mice. Meanwhile, acute myocardial infarction led the significant upregulation of Bcl-2-associated X and downregulation of B-cell lymphoma-2 in the myocardium, and palmatine administration statistically enabled to recover the expression changes of these two apoptosis-related proteins. Moreover, palmatine administration obviously elevated the expression levels of phosphorylated AMP-activated protein kinase and nuclear factor erythroid 2–related factor 2 in the myocardium of acute myocardial infarction–induced mice. In a word, our study indicated that palmatine could protect infarcted myocardium of mice from apoptosis, inflammation, and oxidative stress. Our results suggested that palmatine might be a novel therapeutic agent for acute myocardial infarction. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Palmatine Alleviates Acute Myocardial Infarction Through Activating pAMPK/Nrf2 Signaling Pathway in Mouse Model

Hao

Jiao

2022

Rev. Bras. Farmacogn.

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“…Выявленная отрицательная взаимосвязь с уровнем СРБ и нейтрофилов через 1 год наблюдения может объясняться тем, что хемоаттрактантные свойства IL-16 в отдаленные сроки после ИМБОКА могут быть направлены на Т-регуляторные лимфоциты (Treg), которые оказывают широкий спектр иммуносупрессорных эффектов, таким образом, подавляя развитие воспаления [13]. IL-20, как и IL-16, является провоспалительным цитокином, который обладает атерогенным эффектом, вызывая микроваскулярные поражения, за счет индукции ангиогенеза в гипоксической ткани, а при ОИМ способствует апоптозу кардиомиоцитов и усиливает реперфузионное повреждение миокарда [14,15].…”

Section: Discussionunclassified

Serum cytokines levels in patients with myocardial infarction with non-obstructive and obstructive coronary arteries

et al. 2021

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Aim. To compare the concentrations of proinflammatory and anti-inflammatory cytokines in patients with myocardial infarction with non-obstructive (MINOCA) and obstructive coronary arteries (MIOCA) in the early postinfarction period and after 1-year follow-up.Material and methods. The study included 40 patients with myocardial infarction (experimental group, 19 patients; control group, 21 patients). Three (15,7%) patients with diagnosed acute myocarditis were excluded from the final analysis. Blood samples were taken upon admission, on the 2nd, 4th and 7th days from hospitalization, and also after 1-year follow-up. Twenty-three parameters were analyzed using multiplex analysis and the Multiplex Instrument FLEXMAP 3D system (Luminex Corporation), as well as the MILLIPLEX map Human Cytokine/ Chemokine Panel II.Results. According to multiplex analysis of blood serum of the studied groups, a comparable increase in proinflammatory cytokines CCL-15, CCL-26, CCL-27 in the early postinfarction period and after 1-year follow-up, as well as antiinflammatory and regenerative cytokines CXCL-12, TPO in the early postinfarction period and after 1-year follow-up. In patients with MINOCA, higher concentrations of the following proinflammatory cytokines were determined: IL-16 upon admission (p=0,03), IL-20 on days 2 and 4 of the early postinfarction period (p=0,005 and p = 0.03), as well as CCL-15 on days 4 and 7 (p=0,05 and p=0,02). After 1-year follow-up, among the proinflammatory cytokines, a greater increase in CCL-21 (p=0,02) was noted in the patients of experimental group. Also, in patients with MINOCA, a greater increase in TPO was determined upon admission and on the 2nd day (p=0,02 and p=0,02), SCF — on the 7th day and after 1-year follow-up (p=0,04 and p=0,04), and LIF on the 4th day of early postinfarction period (p=0,007). In contrast, MIOCA patients showed a greater increase in CXCL-12 levels upon admission (p=0,04). At the same time, patients with MINOCA showed a higher level of C-reactive protein on the 1st day, as well as a higher relative monocyte count after 1-year follow-up.Conclusion. Despite a comparable increase in the cytokines CCL-8, CCL-13, CCL26, CCL-27 in patients of both groups, in patients with MINOCA there was a greater increase in proinflammatory cytokines IL-16, IL-20, CCL-15, CCL-21, and also CXCL-12, LIF, TPO, SCF, which have anti-inflammatory and regenerative activity. After 1 year follow-up, MINOCA patients showed a significant increase in CCL-21 and SCF, with a comparable increase in other proinflammatory cytokines in patients of both groups. A greater increase in proinflammatory cytokines in patients with MINOCA may indicate a more aggressive atherosclerosis course and lead to plaque destabilization followed by ischemic event.

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“…In these subtypes, NOX2 abundantly expressing in monocytes is currently accepted as the main source of ROS [29,30]. PKC activation also has been identified to play an important part in inflammation and oxidative stress [31,32]. It has been reported that the cross talk between PKC and NOX could induce NOX-dependent ROS production [33].…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Attenuates LPS-Induced Monocyte-Endothelial Adherence via Inhibiting Cx43/PKC-α/NOX2/ROS Signaling Pathway in Monocytes

Chai

Cao

et al. 2020

Oxidative Medicine and Cellular Longevity

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Dexmedetomidine is widely used for sedating patients in operation rooms or intensive care units. Its protective functions against oxidative stress, inflammation reaction, and apoptosis have been widely reported. In present study, we explored the effects of dexmedetomidine on monocyte-endothelial adherence. We built lipopolysaccharide- (LPS-) induced monocyte-endothelial adherence models with U937 monocytes and human umbilical vein endothelial cells (HUVECs) and observed the effects of dexmedetomidine on U937-HUVEC adhesion. Specific siRNA was designed to knock-down Connexin43 (Cx43) expression in U937 monocytes. Gö6976, GSK2795039, and NAC were used to inhibit PKC-α, NOX2, and ROS, respectively. Then, we detected whether dexmedetomidine could downregulate Cx43 expression and its downstream PKC-α/NOX2/ROS signaling pathway activation and ultimately result in the decrease of U937-HUVEC adhesion. The results showed that dexmedetomidine, at its clinically relevant concentrations (0.1 nM and 1 nM), could inhibit adhesion of molecule expression (VLA-4 and LFA-1) and U937-HUVEC adhesion. Simultaneously, it also attenuated Cx43 expression in U937 monocytes. With the downregulation of Cx43 expression, the activity of PKC-α and its related NOX2/ROS signaling pathway were reduced. Inhibiting PKC-α/NOX2/ROS signaling pathway with Gö6976, GSK2795039, and NAC, respectively, VLA-4, LFA-1 expression, and U937-HUVEC adhesion were all decreased. In summary, we concluded that dexmedetomidine, at its clinically relevant concentrations (0.1 nM and 1 nM), decreased Cx43 expression in U937 monocytes and PKC-α associated with carboxyl-terminal domain of Cx43 protein. With the downregulation of PKC-α, the NOX2/ROS signaling pathway was inhibited, resulting in the decrease of VLA-4 and LFA-1 expression. Ultimately, U937-HUVEC adhesion was reduced.

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IL-20 promotes hypoxia/reoxygenation-induced mitochondrial dysfunction and apoptosis in cardiomyocytes by upregulating oxidative stress by activating the PKC/NADPH oxidase pathway

Cited by 17 publications

References 30 publications

Palmatine Alleviates Acute Myocardial Infarction Through Activating pAMPK/Nrf2 Signaling Pathway in Mouse Model

Palmatine Alleviates Acute Myocardial Infarction Through Activating pAMPK/Nrf2 Signaling Pathway in Mouse Model

Serum cytokines levels in patients with myocardial infarction with non-obstructive and obstructive coronary arteries

Dexmedetomidine Attenuates LPS-Induced Monocyte-Endothelial Adherence via Inhibiting Cx43/PKC-α/NOX2/ROS Signaling Pathway in Monocytes

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