Effect of Salvianolate on Myocardial Ischemia Reperfusion Injury and Its Mechanism

2022 ◽  
Vol 12 (1) ◽  
pp. 226-231
Author(s):  
Liang Fu ◽  
Jinlong Zhao ◽  
Yinkai Ni ◽  
Zhexin Lu ◽  
Zonghui Chen ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Skeletal Structure ◽  
Structure Damage ◽  
Compound C ◽  
Unlabeled Cell ◽  
Myocardial Ischemia Reperfusion ◽  
And Function

<sec> <title>Background:</title> The paper investigated the H9c2 cardiomyocyte model induced by hypoxia. Cell viability was monitored by real-time unlabeled cell function analyzer to determine the levels of LDH, MDA and SOD in cell supernatant. </sec> <sec> <title>Material and Methods:</title> The cytoskeleton staining was labeled by phalloidin staining. WB was applied to detect the expression of myocardial cytoskeleton microtubuleassociated protein and the expression of HIF-1α protein in each group. After adding AMPK inhibitor Compound C, Hoechst 33342 was employed to detect the apoptosis rate of cardiomyocytes, and WB was applied to detect the expressions of myocardial cytoskeleton-associated protein and p-AMPK. </sec> <sec> <title>Results:</title> Salvianolate can effectively improve cell viability, reduce LDH and MDA levels, increase SOD content, improve skeletal structure damage, reduce nuclear concentration, reduce cell debris, and promote the expressions of microtubule-associated protein, α-tubulin and β-tubulin, MAP4, and microfilament-associated protein MLCK, p-MLC-2 in myocardial cytoskeleton microtubules after ischemia and hypoxia. The addition of AMPK inhibitor can inhibit the expressions of p-AMPK, tubulin MAP4, microfilament protein MLCK and p-MLC-2 up-regulated by Salvianolate. </sec> <sec> <title>Conclusion:</title> Salvianolate can promote the expressions of microtubule-associated protein α-tubulin, β-tubulin,MAP4, microfilament-associated protein MLCK and p-MLC-2 in myocardial cytoskeleton after ischemia and hypoxia, indicating that Salvianolate can protect the myocardial cytoskeleton after ischemia and hypoxia, and may protect the structure and function of microtubules and microfilaments in the myocardial cytoskeleton through the AMPK/MAP4 and AMPK/MLCK pathways. </sec>

scholarly journals LncRNA LSINCT5/miR-222 regulates myocardial ischemia‑reperfusion injury through PI3K/AKT pathway

2021 ◽  
Author(s):  
Xueying Tong ◽  
Jiajuan Chen ◽  
Wei Liu ◽  
Hui Liang ◽  
Hezhong Zhu
Keyword(s):  
Myocardial Ischemia ◽  
Cell Viability ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Akt Pathway ◽  
Akt Signaling Pathway ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

AbstractCardiovascular diseases rank the top cause of morbidity and mortality worldwide and are usually associated with blood reperfusion after myocardial ischemia/reperfusion injury (MIRI), which often causes severe pathological damages and cardiomyocyte apoptosis. LSINCT5 expression in the plasma of MI patients (n = 53), healthy controls (n = 42) and hypoxia-reoxygenation (HR)-treated cardiomyocyte AC16 cells was examined using qRT-PCR. The effects of LSINCT5 on cell viability and apoptosis were detected by MTT and flow cytometry, respectively. The expression of apoptosis-related proteins Bcl2, Bax and caspase 3 were tested by Western blot. The interaction between LSINCT5 and miR-222 was predicted by bioinformatic analysis. Moreover, changes in viability and apoptosis of AC16 cells co-transfected with siLSINCT5 and miR-222 inhibitor after HR treatment were examined. At last, the expression of proteins in PI3K/AKT pathway, namely PTEN, PI3K and AKT, was examined to analyze the possible pathway participating in LSINCT5-mediated MI/RI. Our study showed that LSINCT5 expression was upregulated in the plasma of MI patients and HR-treated AC16 cells. LSINCT5 overexpression significantly decreased cell viability and apoptosis. Luciferase reporter gene assay and RNA pulldown assay showed that LSINCT5 was a molecular sponge of miR-222. MiR-222 silencing in AC16 cells simulated the phenotypes of MIRI patients and HR-treated cells, indicating that LSINCT5 functions via miR-222 to regulate proliferation and apoptosis of HR-treated AC16 cells. We also showed that proteins of PI3K/AKT signaling pathway were affected in HR-treated AC16 cells, and LSINTC5 knockdown rescued these effects. LncRNA LSINCT5 was upregulated during MI pathogenesis, and LSINCT5 regulated MIRI possibly via a potential LSINCT5/miR-222 axis and PI3K/AKT signaling pathway. Our findings may provide novel evidence for MIRI prevention.

scholarly journals Follistatin-Like 1 Attenuates Ischemia/Reperfusion Injury in Cardiomyocytes via Regulation of Autophagy

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Weijun Yang ◽  
Qunjun Duan ◽  
Xian Zhu ◽  
Kaiyu Tao ◽  
Aiqiang Dong
Keyword(s):  
Cell Viability ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Annexin V ◽  
Protective Role ◽  
Autophagic Flux ◽  
Rat Cardiomyocytes ◽  
Hypoxia Ischemia ◽  
Myocardial Ischemia Reperfusion

Background. The cardioprotective effect of FSTL1 has been extensively studied in recent years, but its role in myocardial ischemia/reperfusion injury (IRI) is unclear. In this study, we investigated the effect of FSTL1 pretreatment on myocardial IRI as well as the possible involvement of autophagic pathways in its effects. Methods. The effects of FSTL1 on the viability and apoptosis of rat cardiomyocytes were investigated after exposure of cardiomyocytes to hypoxia/ischemia by using the CCK-8 assay and Annexin V/PI staining. Further, western blot analysis was used to detect the effects of FSTL1 pretreatment on autophagy-associated proteins, and confocal microscopy was used to observe autophagic flux. To confirm the role of autophagy, the cells were treated with the autophagy promoter rapamycin or the autophagy inhibitor 3-methyladenine, and cell viability and apoptosis during IRI were observed. These effects were also observed after treatment with rapamycin or 3-methyladenine followed by FSTL1 administration and IRI. Results. FSTL1 pretreatment significantly increased viability and reduced apoptosis in cardiomyocytes exposed to hypoxia/ischemia conditions. Further, FSTL1 pretreatment affected the levels of the autophagy-related proteins and enhanced autophagic flux during IRI. In addition, cell viability was enhanced and apoptosis was decreased by rapamycin treatment, while these effects were reversed by 3-MA treatment. However, when the myocardial cells were pretreated with rapamycin or 3-methyladenine, there was no significant change in their viability or apoptosis with FSTL1 treatment during IRI. Conclusions. FSTL1 plays a protective role in myocardial IRI by regulating autophagy.

scholarly journals Acid sensing ion channel 1a is a key mediator of cardiac ischemia-reperfusion injury

2019 ◽  
Author(s):  
Meredith A. Redd ◽  
Sarah E. Scheuer ◽  
Natalie J. Saez ◽  
Ling Gao ◽  
Mark Hicks ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Ion Channel ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Genetic Locus ◽  
Cardiac Ischemia ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
And Function

AbstractThe proton-gated acid-sensing ion channel 1a (ASIC1a) is implicated in the injury response to cerebral ischemia but little is known about its role in cardiac ischemia. We provide genetic evidence that ASIC1a is involved in myocardial ischemia-reperfusion injury (IRI) and show that pharmacological inhibition of ASIC1a yields robust cardioprotection in rodent and human models of cardiac ischemia, resulting in improved post-IRI cardiac viability and function. Consistent with a key role for ASIC1a in cardiac ischemia, we show that polymorphisms in the ASIC1 genetic locus are strongly associated with myocardial infarction. Collectively, our data provide compelling evidence that ASIC1a is a key target for cardioprotective drugs to reduce the burden of disease associated with myocardial ischemia.

scholarly journals The Role of MCPIP1 in Ischemia/Reperfusion Injury-Induced HUVEC Migration and Apoptosis

2015 ◽  
Vol 37 (2) ◽  
pp. 577-591 ◽  
Author(s):  
Tiebing Zhu ◽  
Qi Yao ◽  
Xiaonan Hu ◽  
Chen Chen ◽  
Honghong Yao ◽  
...  
Keyword(s):  
Cell Migration ◽  
Ischemia Reperfusion Injury ◽  
Umbilical Vein ◽  
Ischemia Reperfusion ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Myocardial Ischemia Reperfusion ◽  
Umbilical Vein Endothelial Cells ◽  
And Function

Background/Aims: Monocyte chemotactic protein-induced protein 1 (MCPIP1) plays a crucial role in various cellular processes, including neurogenesis. However, the relationship between MCPIP1 and myocardial ischemia/reperfusion (I/R) injury remained illdefined. In this study, we explored whether the I/R-mediated up-regulation of MCPIP1 is critical in the modulation of both cell migration and apoptosis in human umbilical vein endothelial cells (HUVECs). Methods: Using Western blot analysis and quantitative real-time PCR, the protein expression and mRNA transcription, respectively, of MCPIP1 was detected in HUVECs. To investigate cell migration, an in vitro scratch assay and a nested matrix model were applied. Results: I/R increased the expression of MCPIP1 via the activation of the mitogen-activated protein kinase (MAPK) and PI3K/Akt pathways. I/R increased migration and apoptosis of HUVECs, which were significantly inhibited by MCPIP1 siRNA. Conclusion: These findings suggest that I/R-mediated up-regulation of MCPIP1 regulates migration and apoptosis in HUVECs. Understanding the regulation of MCPIP1 expression and function may aid in the development of an adjunct therapeutic strategy in the treatment of individuals with I/R injury.

Potential Roles of Siglecs in the Regulation of Allo-Immune Reaction

2019 ◽  
Vol 20 (8) ◽  
pp. 823-828 ◽  
Author(s):  
Songjie Cai ◽  
Jing Zhao ◽  
Takuya Ueno ◽  
Anil Chandraker
Keyword(s):  
Immune Reaction ◽  
Cell Function ◽  
Immune Cell ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Solid Organ Transplantation ◽  
Innate Immune ◽  
Solid Organ ◽  
B Cell Tolerance ◽  
And Function

Siglecs are mammalian sialic acid (Sia) recognizing immuno-globulin-like receptors expressed across the major leukocyte lineages, and function to recognize ubiquitous Sia epitopes on the cell surface. Many Siglecs are inhibitory receptors expressed on innate immune cells, they also have a role in maintaining B cell tolerance as well as modulating the activation of conventional and plasmocytic dendritic cells. Through these and other roles they contribute directly and indirectly to the regulation of T cell function. Siglecs have been identified to play key roles in several forms of blood cancers, autoimmune and infection deceases. So far as we know, there’s no Siglecs related research works on solid organ transplantation. In this review, we describe our understanding of the potential roles of Siglecs in the regulation of immune cell function, which may be crosslinked to allo-rejection and ischemia-reperfusion injury.

scholarly journals N-n-Butyl Haloperidol Iodide Ameliorates Cardiomyocytes Hypoxia/Reoxygenation Injury by Extracellular Calcium-Dependent and -Independent Mechanisms

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Yanmei Zhang ◽  
Gaoyong Chen ◽  
Shuping Zhong ◽  
Fuchun Zheng ◽  
Fenfei Gao ◽  
...  
Keyword(s):  
Cell Viability ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Extracellular Calcium ◽  
Camp Content ◽  
Calcium Dependent ◽  
Reoxygenation Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Pka Pathway ◽  
Hypoxia Reoxygenation

N-n-butyl haloperidol iodide (F2) has been shown to antagonize myocardial ischemia/reperfusion injury by blocking calcium channels. This study explores the biological functions of ERK pathway in cardiomyocytes hypoxia/reoxygenation injury and clarifies the mechanisms by which F2ameliorates cardiomyocytes hypoxia/reoxygenation injury through the extracellular-calcium-dependent and -independent ERK1/2-related pathways. In extracellularcalcium-containing hypoxia/reoxygenation cardiomyocytes, PKCαand ERK1/2 were activated, Egr-1 protein level and cTnI leakage increased, and cell viability decreased. The ERK1/2 inhibitors suppressed extracellular-calcium-containing-hypoxia/reoxygenation-induced Egr-1 overexpression and cardiomyocytes injury. PKCαinhibitor downregulated extracellularcalcium-containing-hypoxia/reoxygenation-induced increase in p-ERK1/2 and Egr-1 expression. F2downregulated hypoxia/reoxygenation-induced elevation of p-PKCα, p-ERK1/2, and Egr-1 expression and inhibited cardiomyocytes damage. The ERK1/2 and PKCαactivators antagonized F2’s effects. In extracellular-calcium-free-hypoxia/reoxygenation cardiomyocytes, ERK1/2 was activated, LDH and cTnI leakage increased, and cell viability decreased. F2and ERK1/2 inhibitors antagonized extracellular-calcium-free-hypoxia/reoxygenation-induced ERK1/2 activation and suppressed cardiomyocytes damage. The ERK1/2 activator antagonized F2’s above effects. F2had no effect on cardiomyocyte cAMP content or PKA and Egr-1 expression. Altogether, ERK activation in extracellular-calcium-containing and extracellular-calcium-free hypoxia/reoxygenation leads to cardiomyocytes damage. F2may ameliorate cardiomyocytes hypoxia/reoxygenation injury by regulating the extracellular-calcium-dependent PKCα/ERK1/2/Egr-1 pathway and through the extracellular-calcium-independent ERK1/2 activation independently of the cAMP/PKA pathway or Egr-1 overexpression.

scholarly journals Inhibition of excessive mitophagy by N-acetyl-L-tryptophan confers hepatoprotection against Ischemia-Reperfusion injury in rats

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8665
Author(s):  
Huiting Li ◽  
Yitong Pan ◽  
Hongjuan Wu ◽  
Shuna Yu ◽  
Jianxin Wang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Structure And Function ◽  
Cell Counting ◽  
Related Protein ◽  
Sprague Dawley ◽  
Hepatic Ischemia ◽  
And Function

In order to investigate the mechnism of hepatoprotective of N-acetyl-L-tryptophan (L-NAT) against ischemia-reperfusion (I/R) injury, the effects of L-NAT were investigated in hepatic ischemia-reperfusion injury (HIRI) models both in vitro and in vivo, which were made by BRL cells and Sprague-Dawley (SD) rats, respectively. The cell viability of hepatocyte was assessed by cell counting kit-8 (CCK-8) staining. The activation of autophagy was detected by electron microscopy (EM), quantitative real-time PCR (qRT-PCR), Western blotting and immunofluorescence. The activation of mitophagy was determined by the change of autophagy related protein, change of mitochondrial structure and function, co-location of autophagy protein and MitoTracker. Results showed that the morphological structures of hepatocytes were changed significantly after HIRI, and the cell viability of hydrogen peroxide (H2O2)-induced BRL cells was decreased. Autophagy markers Beclin1, microtubule associated protein 1 light chain 3-II (LC3-II) and autophagy related protein-7 (ATG-7) were highly expressed and the expression of SQSTM1 (P62) was decreased after HIRI, which suggested that autophagy of hepatocytes was activated after I/R. The reduction of ATP, mitochondrial DNA (mtDNA) and the mitochondrial transmembrane potential (ΔΨm) after H2O2-induced revealed that function of mitochondrial had also undergone significant changes. The increased expression of autophagy protein, destructure of mitochondria and mitochondrial dysfunction, the increased co-location of Beclin1 and MitoTracker induced by H2O2 implied the excessive mitophagy. The expression of the autophagy protein was increased by 3-Methyladenine (3-MA), providing another piece of evidence. Importantly, all changes were restored by L-NAT pretreament. In conclusion, the present findings demonstrate that excessive mitophagy involved in the process of HIRI and L-NAT may protect hepatocytes against HIRI by inhibiting activation of mitophagy and improving the structure and function of mitochondria.

scholarly journals Dexmedetomidine attenuates the injury of H9C2 cardiomyocytes under Hypoxia/reoxygenation condition partly through the inhibition of endoplasmic reticulum stress

2020 ◽  
Author(s):  
Zhipeng Zhu ◽  
Xiaoyan Ling ◽  
Hongmei Zhou ◽  
Caijun Zhang
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Viability ◽  
Cell Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cell Counting ◽  
H9c2 Cells ◽  
Caspase 12 ◽  
Hypoxia Reoxygenation

BackgroundMyocardial ischemia-reperfusion injury (MIRI) has been confirmed to induce endoplasmic reticulum stress(ERS) during downstream cascade reaction when myocardial cell function keep deteriorating to a certain degree. The fact of matter is the clinical inconsistence with experimental outcomes still exist due to the mechanism has not been entirely clarified. Dexmedetomidine (DEX), a new generation anti-inflammatory and organ protector, has been testified can attenuate the IRI of heart. This study aimed to find out if DEX had the capacity to protect the injured cardiomyocytes under in vitro hypoxia/reoxygenation circumstance and if the ERS was totally or partly intervened.MethodsH9C2 cells were subjected to cytotoxicity detection for 24h with DEX normally cultivated in several different concentrations. The proper hypoxia/reoxygenation (H/R) model parameter were concluded by the cell viability and injuries by cell counting kit-8(CCK8) and lactate dehydrogenase (LDH) release, when undergoing hypoxic condition for 3 h and reoxygenated for 3h, 6h,12h, and 24h, respectively. Also, the above index was assessed for H/R cardiomyocytes cultivated by various concentrations of DEX. The apoptosis, expression of) Glucose-regulated protein 78(GRP78), C/EBP homologous protein (CHOP), and caspase-12 were also examined in all groups.Results1, 5 and 10 μM DEX in normal culture could significantly promote the proliferation of H9C2 (> 80%); the activity of H9c2 cells decreased to 62.67% (P < 0.05) at 3h of reoxygenation and to 36% at 6h of reoxygenation followed by 3h anoxic treatment; The cell viability of H9c2 cells in H/R groups incubated with 1 μM DEX increased 61.3%, and the LDH concentration in the supernatant was effectively lowered (−13.7, P < 0.05); H/R dramatically decreased the proportion of flow cytometry apoptosis and increased the expression of GRP78, CHOP and caspase-12, while both DEX and 4-phenyl butyric acid (4-PBA) could significantly reverse those above indicators. Additionally, DEX could induce deeper alterations than 4-PBA on the basis of H/R.Conclusion1 μM DEX can dramatically attended the cell injuries, apoptosis, the expression of GRP78, CHOP and caspase-12 of H9C2 induced by 3h’ hypoxia and 3h’s reoxygenation. moreover, the functions of DEX went beyond the inhibition of ERS under this situation.

scholarly journals Glycine Protects H9C2 Cardiomyocytes from High Glucose- and Hypoxia/Reoxygenation-Induced Injury via Inhibiting PKCβ2 Activation and Improving Mitochondrial Quality

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Yuan Zhang ◽  
Wating Su ◽  
Qiongxia Zhang ◽  
Jinjin Xu ◽  
Huimin Liu ◽  
...  
Keyword(s):  
Cell Viability ◽  
High Glucose ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
H9c2 Cells ◽  
Sod Activity ◽  
Cyt C ◽  
Ldh Release ◽  
Myocardial Ischemia Reperfusion ◽  
Hypoxia Reoxygenation

Background. Patients with diabetes are more vulnerable to myocardial ischemia reperfusion injury (IRI), which is involved in PKCβ2 activation and mitochondrial dysfunction. Glycine has been documented as a cytoprotective agent to attenuate diabetes-related abnormalities and reduce myocardial IRI, but the underlying mechanisms are still unclear. We determined whether glycine could attenuate high glucose- (HG-) and hypoxia/reoxygenation- (H/R-) induced injury by inhibiting PKCβ2 activation and improving mitochondrial quality in cultured H9C2 cells. Methods. H9C2 cells were either exposed to low glucose (LG) or HG conditions with or without treatment of glycine or CGP53353 (a selective inhibitor of PKCβ2) for 48 h, then subjected to 4 h of hypoxia followed by 2 h of reoxygenation (H/R). Cell viability, lactate dehydrogenase (LDH) release, mitochondrial membrane potential (MMP), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) concentration were detected using corresponding commercial kits. Mitochondrial quality control-related proteins (LC-3II, Mfn-2, and Cyt-C) and PKCβ2 activation were detected by Western blot. Results. HG stimulation significantly decreased cell viability and SOD activity and increased LDH release, MDA production, and PKCβ2 activation as compared to LG group, all of which changes were further increased by H/R insult. Glycine or CGP53353 treatment significantly reduced the increase of LDH release, MDA production, PKCβ2 activation, and Cyt-C expression and the decrease of cell viability, SOD activity, MMP, Mfn-2 expression, and LC-3II/LC-3I ratio induced by HG and H/R stimulation. Conclusions. Supplementary glycine protects H9C2 cells from HG- and H/R-induced cellular injury by suppressing PKCβ2 activation and improving mitochondria quality.

Sign in / Sign up

Export Citation Format

Share Document