Background: Lysophosphatidylcholine (lysoPC), a metabolite from membrane phospholipids, accumulates in the ischemic myocardium and plays an important role in the development of myocardial dysfunction ventricular arrhythmia. In this study, we investigated if baicalein, a major component of Huang Qui, can protect against lysoPC-induced cytotoxicity in rat H9c2 embryonic cardiomyocytes.
Methods: Cell viability was detected by the MTT assay; ROS levels were assessed using DCFH-DA; and intracellular free calcium concentrations were assayed by spectrofluorophotometer. Cell apoptosis and necrosis were evaluated by the flow cytometry assay and Hoechst staining. Mitogen-Activated Protein Kinases (MAPKs), which included the ERK, JNK, and p38, and the apoptotic mechanisms including Bcl-2/Bax, caspase-3, caspase-9 and cytochrome c pathways were examined by Western blot analysis. The activation of MAPKs was examined by enzyme-linked immunosorbent assay.
Results: We found that lysoPC induced death and apoptosis of H9c2 cells in a dose-dependent manner. Baicalein could prevent lysoPC-induced cell death, production of reactive oxygen species (ROS), and increase of intracellular calcium concentration in H9c2 cardiomyoctes. In addition, baicalein also inhibited lysoPC-induced apoptosis, with associated decreased pro-apoptotic Bax protein, increased anti-apoptotic Bcl-2 protein, resulting in an increase in the Bcl-2/Bax ratio. Finally, baicalein attenuated lysoPC-induced the expression of cytochrome c, casapase-3, casapase-9, and the phosphorylations of ERK1/2, JNK, and p38. LysoPC-induced ERK1/2, JNK, and p38 activations were inhibited by baicalein.
Conclusions: Baicalein protects cardiomyocytes from lysoPC-induced apoptosis by reducing ROS production, inhibition of calcium overload, and deactivations of MAPK signaling pathways.
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http://dx.doi.org/10.1186/1472-6882-14-233 | DOI Listing |
Viruses
December 2024
Department of Biological Sciences, University of Toledo, 2801 West Bancroft Street, Toledo, OH 43606, USA.
During virus infection, the activation of the antiviral endoribonuclease, ribonuclease L (RNase L), by a unique ligand 2'-5'-oilgoadenylate (2-5A) causes the cleavage of single-stranded viral and cellular RNA targets, restricting protein synthesis, activating stress response pathways, and promoting cell death to establish broad antiviral effects. The immunostimulatory dsRNA cleavage products of RNase L activity (RL RNAs) recruit diverse dsRNA sensors to activate signaling pathways to amplify interferon (IFN) production and activate inflammasome, but the sensors that promote cell death are not known. In this study, we found that DEAH-box polypeptide 15 (DHX15) and retinoic acid-inducible gene I (Rig-I) are essential for apoptosis induced by RL RNAs and require mitochondrial antiviral signaling (MAVS), c-Jun amino terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) for caspase-3-mediated intrinsic apoptosis.
View Article and Find Full Text PDFPathogens
November 2024
Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA.
RNA virus-induced excessive inflammation and impaired antiviral interferon (IFN-I) responses are associated with severe disease. This innate immune response, also referred to as "dysregulated immunity" is caused by viral single-stranded RNA (ssRNA)- and double-stranded-RNA (dsRNA)-mediated exuberant inflammation and viral protein-induced IFN antagonism. However, key host factors and the underlying mechanism driving viral RNA-mediated dysregulated immunity are poorly defined.
View Article and Find Full Text PDFBiomedicines
December 2024
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia.
: Glioblastoma (GB) is a highly aggressive tumor, whose progression is mediated by secretion of extracellular vesicles (EVs), which can pass the brain-blood barrier and be found in the plasma. Here, we performed a comparative analysis of the effects of EVs from the plasma of healthy donors (hEVs) and GB patients before (bEVs) and after (aEVs) tumor surgical resection on invasion of normal astrocytes and GB cells. : We performed the transwell invasion assay, analyzed MAP kinases activation by Western blotting, studied SNAI1/SNAI2 cellular localization by confocal microscopy, measured cadherins expression by flow cytometry, and analyzed secretion of cytokines, which regulate migration and inflammation, by immunoassay.
View Article and Find Full Text PDFClin Transl Med
January 2025
Key Laboratory For Organ Failure Research, Ministry of Education of the People's Republic of China, Guangzhou, China.
Introduction: Heart failure with preserved ejection fraction (HFpEF) is a complex condition characterized by metabolic dysfunction and myocardial lipotoxicity. The roles of PTEN-induced kinase 1 (PINK1) and peroxiredoxin-2 (Prdx2) in HFpEF pathogenesis remain unclear.
Objective: This study aimed to investigate the interaction between PINK1 and Prdx2 to mitigate cardiac diastolic dysfunction in HFpEF.
Cell Biochem Biophys
January 2025
Pharmacy Administration Office, The Third Hospital of Nanchang City, Jiangxi Province, Nanchang, Jiangxi, China.
In the contemporary era of drug discovery, herbal treatments have demonstrated an unparalleled ability to produce anticancer drugs. An important part of the therapy of cancer is the use of plants and their by-products via analogues, which alter the tumor microenvironment and several signaling pathways. The objective of the current investigation was to conclude the rate at which the herbal medications quercetin (QT) and sulforaphane (SFN) repressed the growth of breast carcinoma cells in MDA-MB-231 by preventing the ERK/MAPK signaling systems.
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