CURRENT MOLECULAR MEDICINE
·
2024
·
IF 2.2
Liang Huiqing,Li Huixian,Li Fangjiang,Xiong Xiaobo,Gao Yang
Background: Heart failure (HF) is the ultimate transformation result of
various cardiovascular diseases. Mitochondria-mediated cardiomyocyte apoptosis has
been uncovered to be associated with this disorder.
Objective: This study mainly delves into the mechanism of the anti-arrhythmic drug
amiodarone on mitochondrial toxicity of cardiomyocytes.
Methods: The viability of H9c2 cells treated with amiodarone at 0.5, 1, 2, 3, and 4 μM
was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
assay, and Sigmar1 expression was examined by quantitative real-time PCR (qRTPCR).
After transfection, the viability, apoptosis, reactive oxygen species (ROS) level,
mitochondrial membrane potential (MMP), and potassium voltage-gated channel
subfamily H member 2 (KCNH2) expression in H9c2 cells were assessed by MTT, flow
cytometry, ROS assay kit, mitochondria staining kit, and Western blot.
Results: Amiodarone at 1-4 μM notably weakened H9c2 cell viability with IC50 value of
2.62 ± 0.43 μM. Amiodarone at 0.5-4 μM also evidently suppressed the Sigmar1 level
in H9c2 cells. Amiodarone repressed H9c2 cell viability and KCNH2 level and triggered
apoptosis, ROS production and mitochondrial depolarization, while Sigmar1 upregulation
reversed its effects. Moreover, KCNH2 silencing neutralized the combined
modulation of amiodarone and Sigmar1 up-regulation on H9c2 cell viability, apoptosis,
and ROS production.
Conclusion: Amiodarone facilitates the apoptosis of H9c2 cells by restraining Sigmar1
expression and blocking KCNH2-related potassium channels.
研究领域:
心脏病学
·
药理学
·
细胞生物学
·
分子生物学
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DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2019
·Vol. 411
·期 18
·4025-4030
·
IF 3.286
Li Hao-Wen,Hua Xin,Long Yi-Tao
Time-of-flight secondary ion mass spectrometry (ToF-SIMS) has shown promising applications in single-cell analysis owing to its high spatial resolution molecular imaging capability. One of the main drawbacks hindering progress in this field is the relatively low ionization efficiency for biological systems. The complex chemical micro-environment in single cells typically causes severe matrix effects, leading to significant signal suppression of biomolecules. In this work, we investigated the signal enhancement effect of graphene quantum dots (GE QDs) in ToF-SIMS analysis. A × 160 magnification of ToF-SIMS signal for amiodarone casted on glass slide was observed by adding amino-functionalized GE QDs (amino-GE QDs), which was significantly higher than adding previously reported signal enhancement materials and hydroxyl group-functionalized GE QDs (hydroxyl-GE QDs). A possible mechanism for GE QD-induced signal enhancement was proposed. Further, effects of amino-GE QDs and hydroxyl-GE QDs on amiodarone-treated breast cancer cells were compared. A significant signal improvement for lipids and amiodarone was achieved using both types of GE QDs, especially for amino-GE QDs. In addition, ToF-SIMS chemical mapping of single cells with better quality was obtained after signal enhancement. Our strategy for effective ToF-SIMS signal enhancement holds great potential for further investigation of drug metabolism pathways and the interactions between the cell and micro-environment.
研究领域:
分析化学
·
生物医学工程
·
材料科学
·
细胞生物学
·
药学
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2026
·
IF 5.2
Xiao Li,Xuanwei Li,Caixia Yan,Yaokun Xia,Keke Huang,Jia Chen
Alkyl carboxylic acid–HFIP SUPRAS was developed as an ideal extractant for HF-LPME. • Reversed micellar SUPRAS forms with low HFIP and is stable at low salt levels. • Hollow fiber and restricted-access SUPRAS synergistically reduce matrix effects. • Multiclass antiarrhythmic drugs in human plasma are detected by LC-MS/MS. • Low solvent/sample consumption and an AGREEprep score of 0.5 ensure eco-friendliness. An alkyl carboxylic acid–hexafluoroisopropanol (HFIP) supramolecular solvent (SUPRAS) was developed as a restricted-access solvent for hollow fiber liquid-phase microextraction (HF-LPME) and applied to the determination of seven antiarrhythmic drugs (mexiletine, propranolol, diltiazem, amlodipine, propafenone, verapamil, and amiodarone) in human plasma. SUPRAS formation required only a low HFIP dosage (<10%, v /v for alkyl carboxylic acid ≤4%, w / v ) and was minimally affected by low ionic strength (NaCl <50 mM) or low organic solvent content (methanol <5%, v /v). The SUPRAS consisted of reversed micellar aggregates with hydrophobic outer surfaces and hydrophilic inner cavities. The SUPRAS exhibited restricted-access behavior, efficiently excluding macromolecular proteins (extraction efficiency <18.3%, solubility <4.5 mg mL −1 ) via the synergistic effects of protein denaturation/flocculation induced by HFIP and octanoic acid and size exclusion by the SUPRAS matrix. After systematic optimization, the proposed method coupled with high-performance liquid chromatography-tandem mass spectrometry demonstrated acceptable analytical performance. Satisfactory linearity was achieved, with correlation coefficients ranging from 0.9903 to 0.9997. Method limits of detection (S/N = 3) ranged from 0.01 to 0.10 μg L −1 , while method limits of quantification (S/ N = 10) were 0.03–0.33 μg L −1 . Acceptable recoveries were obtained for spiked samples (86.5–126.6%), with only two analytes slightly exceeding 130% at the low concentration level, and intra- and inter-day precisions were below 19.3%. Owing to the combined microfiltration capability of the hollow fiber and the restricted-access properties of the SUPRAS, the method exhibited manageable matrix effects (70.6–132.5%) and eliminated the need for a separate protein precipitation step, while consuming only 25 μL of SUPRAS per extraction. Greenness assessment using AGREEprep software yielded a score of 0.5, confirming satisfactory eco-friendliness and sustainability. This SUPRAS-HF-LPME method is simple, efficient, and environmentally benign, serving as a promising pretreatment and quantification strategy for antiarrhythmic drugs in complex human plasma matrices. Download: Download high-res image (265KB) Download: Download full-size image
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高影响因子
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