Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 471 - 486
Published: Jan. 1, 2024
Language: Английский
Basic Research in Cardiology, Journal Year: 2023, Volume and Issue: 118(1)
Published: Oct. 5, 2023
Abstract Mitochondrial function is maintained by several strictly coordinated mechanisms, collectively termed mitochondrial quality control including fusion and fission, degradation, biogenesis. As the primary source of energy in cardiomyocytes, mitochondria are central organelle for maintaining cardiac function. Since adult cardiomyocytes humans rarely divide, number dysfunctional cannot easily be diluted through cell division. Thus, efficient degradation crucial to cellular Mitophagy, a specific form autophagy, major mechanism which damaged or unnecessary targeted eliminated. Mitophagy active at baseline response stress, plays an essential role cardiomyocytes. mediated multiple mechanisms heart, each these can partially compensate loss another mechanism. However, insufficient levels mitophagy eventually lead dysfunction development heart failure. In this review, we discuss molecular pathophysiology, with focus on recent findings field.
Language: Английский
Citations
49
International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(13), P. 5145 - 5161
Published: Jan. 1, 2024
Non-small cell lung cancer (NSCLC), a major subtype of cancer, encompasses squamous carcinoma, adenocarcinoma, and large carcinoma. Compared to small NSCLC cells grow divide more slowly, their metastasis occurs at later stage. Currently, chemotherapy is the primary treatment for this disease. Sappanone A (SA) flavonoid compound extracted from plant Caesalpinia sappan, known its antitumor, redox-regulating, anti-inflammatory properties. Recent studies have investigated interaction SA with mitochondrial pathways in regulating death through Nrf-2/GPX-4/xCT axis. This study specifically explores mechanism by which affects morphology structure regulation mitophagy biogenesis tumor cells. The primarily utilizes second-generation transcriptomic sequencing data molecular docking techniques elucidate role programmed omics results indicate that significantly targets genes involved oxidative phosphorylation, mitophagy, dynamics, stress. Further findings confirmed Nrf-2/GPX4/xCT pathway serves as crucial target NSCLC. Knockdown Nrf-2 (si-Nrf-2) overexpression (ad-Nrf-2) were shown modulate therapeutic efficacy varying degrees. Additionally, modifications GPX4/xCT affected regulatory effects on autophagy, biogenesis, energy metabolism. These mechanisms may be mediated caspase ferroptosis-related signaling. Molecular biology experiments demonstrated intervention further inhibits phosphorylation FUNDC1 Tyr18 downregulates TOM20 expression. was found reduce expression PGC1α, Nrf-1, Tfam, resulting decrease respiration Overexpression counteract biogenesis. Confocal microscopy revealed increases fragmentation, subsequently inducing pathway-mediated death. However, genetic modification altered In conclusion, has been identified promising agent apoptosis ferroptosis represent key Targeting axis offers novel approach maintaining homeostasis within cellular microenvironment.
Language: Английский
Citations
14
Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 1, 2024
Septic cardiomyopathy (SCM) is a complication of myocardial injury in patients with severe sepsis. This study highlights the potential Astragaloside IV(AS) treatment septic and provides reference for developing cardioprotective drugs targeting DUSP1-PHB2-related mitochondria-ER interaction. Dual specificity phosphatase-1 (DUSP1)/Prohibitin 2 cardiomyocyte-specific knockout mice (DUSP1/PHB2CKO) /DUSP1 transgenic (DUSP1/PHB2TG) were used to generate LPS-induced sepsis models. The pathological mechanism by which AS-IV improves heart was detected using cardiac ultrasound, fluorescence staining, transmission electron microscopy, western blotting. After siRNA cardiomyocytes DUSP-1/PHB2, changes mitochondrial function morphology determined qPCR, blotting, ELISA, laser confocal targeted therapeutic effects further examined. SCM leads dysfunction. However, IV (AS) normalizes homeostasis ER function. Notably, protective effect blocked DUSP1/Prohibitin but remained unaffected DUSP1 (DUSP1/PHB2TG). AS DUSP1-PHB2 related
Language: Английский
Citations
6
Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e28921 - e28921
Published: March 29, 2024
Diabetic cardiomyopathy is one common cardiovascular complication without effective treatments. Dihydromyricetin (DHY), a natural dihydroflavonol compound extracted from Ampelopsis grossedentata, possesses versatile pharmacologically important effects. In our current research, we planned to evaluate the impact and probable DHY mechanisms in high glucose (HG)-induced cardiomyocytes. Primary cardiomyocytes were pretreated with different concentrations of (0, 20, 40, 80, 160, 320 μM) for various time 1, 2, 4, 12, 24 h). They then stimulated 48 h 5.5 mmol/L normal (NG) 33.3 (HG). Cell viability, adenosine-triphosphate (ATP) levels, lactate dehydrogenase (LDH) release detected. JC-1 staining was employed measure mitochondrial membrane potential. MitoSOX dihydroethidium (DHE) applied oxidative stress levels. TDT mediated dUTP nick end labeling (TUNEL) used apoptotic Expressions calcium/calmodulin-dependent protein kinase II (CaMKII), phospholamban (PLB), optic atrophy 1 (OPA1), dynamin-related (DRP1), caspase 3, mixed lineage domain like (MLKL), receptor interacting 3 (RIPK3), (RIPK1) detected by immunofluorescence and/or Western blot. improved cell enhanced ATP level, decreased LDH content HG-stimulated cardiomyocytes, suggesting attenuating injury. reduced number TUNEL positive cells, inhibited RIPK3 cleaved-caspase expression, implying alleviated necroptosis diminished monomers, DHE fluorescence intensity as well DRP1 expression but increased aggregates OPA1 indicating that attenuated also CaMKII activity suppressed PLB phosphorylation oxidation HG-induced injury wherein necroptosis, repressed ROS production, oxidation, may serve potential agent prevent treat diabetic cardiomyopathy.
Language: Английский
Citations
4
International Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: 21(7), P. 1194 - 1203
Published: Jan. 1, 2024
This study aims to elucidate the roles of Phosphoglycerate Mutase Family Member 5 (Pgam5) and Prohibitin 2 (Phb2) in context hyperglycemia-induced myocardial dysfunction, a critical aspect diabetic cardiomyopathy.The research employed primary cardiomyocytes, which were then subjected hyperglycemia treatment mimic conditions.We used siRNA transfection knock down Pgam5 overexpressed Phb2 using adenovirus assess their individual combined effects on cardiomyocyte health.Mitochondrial function was evaluated through measurements mitochondrial membrane potential JC-1 probe, levels reactive oxygen species (ROS) assessed.Additionally, involved qPCR analysis quantify transcriptional changes genes related fission mitophagy.Our findings indicate that significantly reduces viability impairs function, as evidenced by decreased increased ROS levels.Pgam5 knockdown observed mitigate these adverse effects, preserving viability.On molecular level, found regulate associated with (such Drp1, Mff, Fis1) mitophagy (including Parkin, Bnip3, Fundc1).Furthermore, overexpression countered dysfunction normalized key antioxidant enzymes.The data suggest protective role for both against cellular damage.The elucidates regulating dynamics setting dysfunction.By modulating mitophagy, emerge players integrity health under conditions.These contribute our understanding mechanisms underlying cardiomyopathy therapeutic targets mitigating diabetes.
Language: Английский
Citations
3
International Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: 21(13), P. 2464 - 2479
Published: Jan. 1, 2024
MAPKK4 has been implicated in the pathological mechanisms underlying myocardial and vascular injury, specifically influencing endothelial cell damage programmed death via subcellular pathways. Nevertheless, regulatory role of coronary microvascular injury following infarction remains unconfirmed, exploration targeted mitochondrial protective therapeutic agents unaddressed. In light this gap, we established a gene-modified mouse model ischemia-reperfusion employed Buyang Huanwu decoction (BYHW), traditional cardiovascular formula, to assess its efficacy treating post-ischemia-reperfusion. The study aimed elucidate mechanism by which BYHW mitigates induced through attenuation apoptosis. Experimental outcomes revealed that high-dose significantly ameliorated post-ischemia-reperfusion, restoring structural integrity microvasculature reducing inflammation oxidative stress. Contrarily, transgenic mice overexpressing MAPKK4, intervention failed attenuate To further investigate, simulated hypoxia/reoxygenation cells using MAPKK4-related cellular gene modification model. results indicated attenuates inflammatory enhances viability hypoxic stress, inhibiting apoptosis pathway. However, overexpression MAPKK4/p38 negated effects BYHW, showing no impact on stress under conditions. Molecular interaction studies confirmed active components Astragaloside IV Ligustrazine, interact with MAPKK4/P38 axis.
Language: Английский
Citations
2
Morphology, Journal Year: 2024, Volume and Issue: 161(4), P. 95 - 111
Published: June 17, 2024
The pathomorphogenesis of hypertrophic cardiomyopathy is a disruption the arrangement muscle cell bundles in myocardium and associated with mutations genes encoding synthesis myocardial contractile proteins. Metabolic changes this pathology are caused by hypertrophy interventricular septum due to apparatus these mitochondrial dysfunction. Myofiber protein can negatively affect mitochondria through increased oxidative stress ATP demand. complex organelles circular DNA enzyme complexes involved redox reactions, which cause frequent damage structures membranes reactive oxygen species. In regard, dysfunction be also proteins, leads mitophagy dynamics. functioning defective insufficient ineffective contraction, same consequences at tissue level as genes. review, we tried summarize role cardiomyopathy.
Language: Английский
Citations
0
Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 471 - 486
Published: Jan. 1, 2024
Language: Английский
Citations
0