Iminostilbene, a novel small-molecule modulator of PKM2, suppresses macrophage inflammation in myocardial ischemia–reperfusion injury

Lu, Shan; Tian, Yu; Luo, Yun; Xu, Xudong; Ge, Wenxiu; Sun, Guibo; Sun, Xiaobo

doi:10.1016/j.jare.2020.09.001

Cited by 30 publications

(23 citation statements)

References 57 publications

(41 reference statements)

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“…Inflammation was a key factor in the MI/R injury [ 21 ], and oxidative stress was also closely related to inflammation. IL-6 was significantly increased during hypoxia in cardiomyocytes [ 22 ], while iNOS is a classical inflammatory factor.…”

Section: Resultsmentioning

confidence: 99%

Protective Effect of Sufentanil on Myocardial Ischemia-Reperfusion Injury in Rats by Inhibiting Endoplasmic Reticulum Stress

Qiu

Zhong

Hou

et al. 2022

Computational and Mathematical Methods in Medicine

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Objective. Sufentanil is the most common drug in clinical practice for the treatment of ischemic heart disease. This study is to investigate the protective mechanism of sufentanil on rat myocardial ischemia-reperfusion (I/R) injury. Methods. A rat I/R model was established by ligating the left anterior descending coronary artery. A total of 24 SD male rats were enrolled and divided randomly into the control group, I/R group, sufentanil group (SUF; 3 μg/kg), and diltiazem group (DLZ; 20 mg/kg; positive control). The rat hearts were subjected to 30 min of ischemia followed by 120 min of reperfusion. Subsequently, hemodynamics, pathological changes of myocardial tissue, serum biochemical parameters, oxidative stress factors, the level of serum inducible nitric oxide synthases (iNOS), interleukin-6 (IL-6), and other bioactive factors were analyzed in the rats. Result. Compared with the I/R group, sufentanil significantly improved cardiac action, myocardial fiber, and cardiomyocyte morphology and reduced inflammatory cell infiltration in rats in the SUF group. And the level of creatine kinase isoenzyme (CK-MB), troponin (cTn), lactate dehydrogenase (LDH), malondialdehyde (MDA), iNOS, and IL-6 was significantly declined in the serum of SUF group, while the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were significantly activated in the myocardial tissues. In addition, sufentanil also significantly decreased the protein expression of GRP78, CHOP, Caspase 12, and ATF6 in the myocardial tissue of the SUF group. Conclusion. Sufentanil has a significant protective activity on myocardial I/R injury in rats, the mechanism of which may be associated with the inhibition of endoplasmic reticulum stress and oxidative stress.

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Section: Resultsmentioning

confidence: 99%

Protective Effect of Sufentanil on Myocardial Ischemia-Reperfusion Injury in Rats by Inhibiting Endoplasmic Reticulum Stress

Qiu

Zhong

Hou

et al. 2022

Computational and Mathematical Methods in Medicine

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“…24 Recombinant PKM2 confers neuroprotective effects against ischemic damages, 25 and iminostilbene binds to PKM2 to reduce myocardial infarction, and improves cardiac function in rats with myocardial ischemia/reperfusion injury model. 26 Therefore, PKM2 might be involved in JMJD5/HIF-1α-mediated protective effect against myocardial infarction. However, further investigation will be required to elucidate this.…”

Section: Discussionmentioning

confidence: 99%

JMJD5 attenuates oxygen–glucose deprivation and reperfusion‐induced injury in cardiomyocytes through regulation of HIF‐1α‐BNIP3

Zhang

Pang

Liu

et al. 2021

The Kaohsiung J of Med Scie

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Proteins in Jumonji family function as histone demethylases and participate in cardiac development. Jumonji domain containing 5 (JMJD5) is responsible for the embryonic development through removing methyl moieties from H3K36me2 histone, and has proproliferative effect on heart and eye development. However, the protective role of JMJD5 against oxygen-glucose deprivation and reperfusion (OGD/R)-induced injury in cardiomyocytes has not been fully understood. Firstly, myocardial ischemia/reperfusion (I/R) rat model was established by ligation of left coronary artery. OGD/R was performed in non-transfected H9C2 or H9C2 transfected with pcDNA-JMJD5 plasmid to induce cell cytotoxicity. Data from qRT-PCR and western blot showed that JMJD5 was reduced in the heart tissues of myocardial I/R rat model and OGD/R-induced H9C2. Secondly, JMJD5 over-expression attenuated OGD/R-induced decrease in cell viability and increase in lactate dehydrogenase secretion and cell apoptosis in H9C2. Mitophagy was promoted by pcDNA-mediated over-expression of JMJD5 with enhanced protein expression of LC3-I, LC3-II, Atg5, and Beclin 1. Thirdly, knockdown of JMJD5 aggravated OGD/Rinduced decrease in hypoxia-inducible factor-1α (HIF-1α), whereas JMJD5 overexpression enhanced BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein) through upregulation of HIF-1α. Lastly, BNIP3 silencing promoted cell apoptosis, suppressed mitophagy, and attenuated the protective effects of JMJD5 over-expression against OGD/R-induced injury in H9C2. In conclusion, JMJD5 exerted protective effects against OGD/R-induced injury in cardiomyocytes through upregulation of HIF-1α-BNIP3.

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“…Inflammatory response is a very complex biological process, which has an important role in many diseases ( Costa et al., 2021 ; Li et al., 2021 ; Lu et al., 2021 ; Wang J. et al., 2021 ). Previous studies showed that inflammatory response played a critical role in the onset of depression, and the disturbance of inflammation levels could increase the incidence of depression ( Leonard, 2018 ; Colasanto et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota-Related Inflammation Factors as a Potential Biomarker for Diagnosing Major Depressive Disorder

Bai

et al. 2022

Front. Cell. Infect. Microbiol.

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ObjectiveAlthough many works have been done, the objectively measured diagnostic biomarkers are not available. Thus, we conducted this study to identify potential biomarkers for objectively diagnosing depression and explore the role of gut microbiota in the onset of depression.MethodsMajor depressive disorder (MDD) patients (n=56) and demographic data-matched healthy controls (HCs) (n=56) were included in this study. The gut microbiota in fecal samples and inflammation-related factors in serum were measured. Both univariate and multivariate statistical analyses were performed to identify the differential gut microbiota and inflammation-related factors.ResultsFinally, 46 differential operational taxonomic units (OTUs) (60.9% OTUs belonging to Firmicutes) and ten differential inflammation-related factors were identified. Correlation analysis showed that there were significant correlations between 14 differential OTUs (9 OTUs belonging to Firmicutes and 5 OTUs belonging to family Lachnospiraceae under Firmicutes) and seven differential inflammation-related factors. Meanwhile, 14 differential OTUs (9 OTUs belonging to Firmicutes and 5 OTUs belonging to family Lachnospiraceae under Firmicutes) and five differential inflammation-related factors (adiponectin, apolipoprotein A1, alpha 1-antitrypsin, neutrophilicgranulocyte count/white blood cell count and basophil count) were significantly correlated to depression severity. A panel consisting of these five differential inflammation-related factors could effectively diagnose MDD patients from HCs.ConclusionsOur results suggested that Firmicutes, especially family Lachnospiraceae, might play a role in the onset of depression via affecting the inflammation levels of host, and these five differential inflammation-related factors could be potential biomarkers for objectively diagnosing MDD.

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Iminostilbene, a novel small-molecule modulator of PKM2, suppresses macrophage inflammation in myocardial ischemia–reperfusion injury

Abstract: Graphical abstract

Cited by 30 publications

References 57 publications

Protective Effect of Sufentanil on Myocardial Ischemia-Reperfusion Injury in Rats by Inhibiting Endoplasmic Reticulum Stress

Protective Effect of Sufentanil on Myocardial Ischemia-Reperfusion Injury in Rats by Inhibiting Endoplasmic Reticulum Stress

JMJD5 attenuates oxygen–glucose deprivation and reperfusion‐induced injury in cardiomyocytes through regulation of HIF‐1α‐BNIP3

Gut Microbiota-Related Inflammation Factors as a Potential Biomarker for Diagnosing Major Depressive Disorder

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