OBJECTIVETo study the role of Ca2+ overload and energy metabolism in mitochondria in masticatory muscle dysfunctional induced by occlusal trauma.

METHODSMitochondrial Ca2+ contents were measured with atomic emission spectrophotometer. Mitochondrial ATP and ADP contents were measured with high performance liquid chromatography.

RESULTS(1) Mitochondrial Ca2+ contents of masseter muscle ipsilateral to metal splint in ten and twenty days' experimental groups and that contralateral to metal splint in twenty days' experimental group increased significantly (P < 0.05). (2) Mitochondrial ATP contents of masseter muscle ipsilateral to metal splint in experimental groups were higher than that in control groups and contralateral to metal splint after twenty days. (3) Mitochondrial Ca2+ contents of masseter muscle ipsilateral to metal splint were significantly negatively correlated to the mitochondrial ATP contents (r = -0.780, P < 0.05).

CONCLUSIONCa2+ overload in mitochondria depresses ATP production, which results in energy metabolism disorder in masticatory muscle cells. It may play an important role in the mechanism that occlusal trauma results in masticatory muscle dysfunction.

Adenosine Diphosphate ; chemistry ; Adenosine Triphosphate ; chemistry ; Animals ; Calcium ; chemistry ; Energy Metabolism ; Masseter Muscle ; chemistry ; injuries ; Mitochondria, Muscle ; chemistry ; Rabbits

PURPOSE: This study was designed to investigate whether valproic acid(VPA) induces Reye's syndrome by analyzing blood chemistry, carnitine(CARN) concentration, and the morphologic changes of hepatocytes. The changes of GFAP immunoreactivity of astrocytes were examined in rats with Reye's syndrome induced by VPA. And the effects of CARN supplementation on Reye's syndrome were also investigated. METHODS: Ten rats were assigned to each of the following 3 groups : control group(0.5ml of normal saline), VPA group(250mg/kg of VPA), and VPA plus CARN group(250mg/kg of VPA and 100mg/kg of CARN). Each dose was injected intraperitoneally every 12 hours for 7 days. All rats fasted overnight following the final injection. RESULTS: In the VPA group, the levels of glucose and ketones decreased and the levels of ammonia, SGOT and lactates increased as compared with the control group. Lower levels of free CARN and higher acyl/free CARN ratios, indicating secondary CARN deficiency, were observed, and the appearance of transformed mitochondria of hepatocytes provided further evidence of mitochondrial metabolic dysfunction in Reye's syndrome. The GFAP immunoreactivity and the area percent of GFAP-positive astrocytes in the cingulum decreased in VPA group. In the VPA plus CARN group, there were no significant differences with the control group in blood chemistry, acyl/free CARN ratios and morphology of hepatocytes. However, the GFAP immunoreativity and the percent of GFAP-positive astrocytes in the cingulum decreased as much as in the VPA group. CONCLUSION: It is suggested that CARN supplementation may prevent abnormal findings of blood chemistry, CARN deficiency and the morphologic changes of liver mitochondria due to VPA, but CARN may have little effect on GFAP immunoreactivity of astrocytes in rats with Reye's syndrome induced by VPA.
Ammonia ; Animals ; Aspartate Aminotransferases ; Astrocytes* ; Carnitine* ; Chemistry ; Glucose ; Hepatocytes ; Ketones ; Lactates ; Mitochondria ; Mitochondria, Liver ; Rats* ; Reye Syndrome* ; Valproic Acid*

Artemisia argyi (A. argyi), a plant with a longstanding history as a raw material for traditional medicine and functional diets in Asia, has been used traditionally to bathe and soak feet for its disinfectant and itch-relieving properties. Despite its widespread use, scientific evidence validating the antifungal efficacy of A. argyi water extract (AAWE) against dermatophytes, particularly Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum, remains limited. This study aimed to substantiate the scientific basis of the folkloric use of A. argyi by evaluating the antifungal effects and the underlying molecular mechanisms of its active subfraction against dermatophytes. The results indicated that AAWE exhibited excellent antifungal effects against the three aforementioned dermatophyte species. The subfraction AAWE6, isolated using D101 macroporous resin, emerged as the most potent subfraction. The minimum inhibitory concentrations (MICs) of AAWE6 against T. rubrum, M. gypseum, and T. mentagrophytes were 312.5, 312.5, and 625 μg·mL^-1, respectively. Transmission electron microscopy (TEM) results and assays of enzymes linked to cell wall integrity and cell membrane function indicated that AAWE6 could penetrate the external protective barrier of T. rubrum, creating breaches ("small holes"), and disrupt the internal mitochondrial structure ("granary"). Furthermore, transcriptome data, quantitative real-time PCR (RT-qPCR), and biochemical assays corroborated the severe disruption of mitochondrial function, evidenced by inhibited tricarboxylic acid (TCA) cycle and energy metabolism. Additionally, chemical characterization and molecular docking analyses identified flavonoids, primarily eupatilin (131.16 ± 4.52 mg·g^-1) and jaceosidin (4.17 ± 0.18 mg·g^-1), as the active components of AAWE6. In conclusion, the subfraction AAWE6 from A. argyi exerts antifungal effects against dermatophytes by disrupting mitochondrial morphology and function. This research validates the traditional use of A. argyi and provides scientific support for its anti-dermatophytic applications, as recognized in the Chinese patent (No. ZL202111161301.9).
Antifungal Agents/chemistry* ; Arthrodermataceae ; Artemisia/chemistry* ; Molecular Docking Simulation ; Mitochondria ; Microbial Sensitivity Tests

Animals ; Cell Respiration ; Electron Transport Complex III ; metabolism ; Humans ; Iron-Sulfur Proteins ; chemistry ; metabolism ; Mitochondria ; metabolism ; Peptide Fragments ; chemistry ; metabolism ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Subunits ; chemistry

AIMTo study the inhibition of oxygen consumption by annonaceous acetogenins (ACG) and their structure-activity relationship (SAR).

METHODSThe inhibition of oxygen consumption in chicken liver cell respiration by different structural ACG was studied by using oxygen electrode technique.

RESULTSSix ACG showed potent inhibitory effects like rotenone which was a classical inhibitor of mitochondrial complex I, and was more potent than complex IV inhibitor KCN. The IC50 values of six ACG for inhibiting oxygen consumption suggested that bistetrahydrofuran (THF) ACG was 7-11 times more active than non-THF ACG, and A1-type ACG was more potent than A2-type ACG.

CONCLUSIONThe terminal gamma-lactone was crucial for the inhibition of oxygen consumption. The distance between THF and gamma-lactone, the hydroxyl groups in the alkyl chain, were the important factors of SAR, but the 4-OH group possibly played some negative role in the exhibit of potent activity.

Acetogenins ; Animals ; Annona ; chemistry ; Cell Separation ; Chickens ; Fatty Alcohols ; chemistry ; pharmacology ; Furans ; chemistry ; isolation & purification ; pharmacology ; Lactones ; chemistry ; isolation & purification ; pharmacology ; Liver ; cytology ; Mitochondria, Liver ; drug effects ; metabolism ; Oxygen Consumption ; drug effects ; Plants, Medicinal ; chemistry ; Seeds ; chemistry ; Structure-Activity Relationship

As a kind of mitochondrial membrane protein with protein kinase activity, phosphatase and tensin homolog deleted on chromosome ten induced kinase 1 (PINK1) is involved in many biological metabolic processes. Since PINK1 had been found to be associated with Parkinson's disease, researchers have been exploring its biological function. PINK1 localizes in the outer mitochondrial membrane and regulates cell function through phosphorylating proteins. PINK1 is involved in mitochondrial function, mitochondrial morphology and mitochondrial autophagy, but the regulatory pathway is not yet clear. PINK1 is expressed widely in many tissues with a variety of biological activity, especially in tissues with high energy consumption. It may therefore be involved in the development and regulation of many diseases. Mutations in PINK1 were originally discovered to cause autosomal recessive Parkinson's disease. Recently some research has revealed that PINK1 is related to the development of neonatal hypoxic-ischemic encephalopathy, cancer, diabetes and other diseases. Studying and exploring the biological functions of PINK1 will facilitate the identification of the targets for therapeutic intervention for its related diseases. This review article mainly focuses on recent studies about the biological function and related diseases of PINK1.
Autophagy ; Diabetes Mellitus, Type 2 ; etiology ; Humans ; Hypoxia-Ischemia, Brain ; etiology ; Mitochondria ; physiology ; Neoplasms ; etiology ; Protein Kinases ; chemistry ; physiology

Apoptosis ; Down-Regulation ; Electron Transport Complex IV ; chemistry ; genetics ; metabolism ; Humans ; Mitochondria ; metabolism ; Mutation ; Neoplasms ; genetics ; metabolism ; pathology

The mitochondrial respiratory chain consists of 5 enzyme complexes that are responsible for ATP generation. The paradigm of the electron transport chain as discrete enzymes diffused in the inner mitochondrial membrane has been replaced by the solid state supercomplex model wherein the respiratory complexes associate with each other to form supramolecular complexes. Defects in these supercomplexes, which have been shown to be functionally active and required for forming stable respiratory complexes, have been associated with many genetic and neurodegenerative disorders demonstrating their biomedical significance. In this review, we will summarize the functional and structural significance of supercomplexes and provide a comprehensive review of their assembly and the assembly factors currently known to play a role in this process.
Adenosine Triphosphate ; metabolism ; Arylamine N-Acetyltransferase ; metabolism ; Cardiolipins ; metabolism ; Electron Transport ; Humans ; Mitochondria ; enzymology ; metabolism ; Multienzyme Complexes ; chemistry ; metabolism

The cellular toxicities of surfactants, a solvent, and an antifreeze that are included in herbicide formulations were assessed by measuring their effects on membrane integrity, metabolic activity, mitochondrial activity, and total protein synthesis rate in a cell culture. Polyethylene glycol, propylene glycol, and monoethylene glycol exhibited no cellular toxicity even at a high concentration of 100 mM. Sodium lauryl ether sulfate and polyoxyethylene lauryl ether significantly damaged the membrane, disturbed cellular metabolic activity, and decreased mitochondrial activity and the protein synthesis rate; however, their toxicity was far below those of the severely toxic chemicals at comparable concentrations. The severely toxic category included polyoxypropylene glycol block copolymer, polyoxyethylene tallow amine, and polyoxyethylene lauryl amine ether. These surfactants were cytotoxic between 3.125 microM and 100 microM in a dose-dependent manner. However, the toxicity graph of concentration vs toxicity had a point of inflection at 25 microM. The slope of the toxicity graph was gentle when the concentration was below 25 microM and steep when the concentration was greater than 25 microM. In conclusion, our results suggest that the toxicity of surfactants be taken care of pertinent treatment of acute herbicide intoxication.
Animals ; Cell Line ; Cell Membrane/drug effects ; Herbicides/*chemistry ; Mice ; Mitochondria/drug effects ; Polyethylene Glycols/toxicity ; Sodium Dodecyl Sulfate/toxicity ; Surface-Active Agents/chemistry/*toxicity ; Toxicity Tests

Ferulic acid (FA) was loaded into liposomes via calcium acetate gradient with (80.2 +/- 5.2)% entrapment efficiency. The average sizes of blank liposome and FA liposome were about 155 nm and 154 nm, respectively. The zeta potential of blank liposome and FA liposome were (13.14 +/- 1.67) mV and (4.12 +/- 0.05) mV, respectively. Unilamellar vesicles were present in freeze-fracture electron microscopy. In the pharmacodynamic studies, the protective effect of liposomal ferulic acid on tBHP-challenged U937 cells was measured with the morphology of cell injury, mitochondrial transmembrane potential alternation and cell viability assay used as index. The results of MTT assay, microscopy indicated that FA liposomes exhibited greater antioxidant activity than FA solution on U937 cell.
Antioxidants ; administration & dosage ; pharmacology ; Cholesterol ; chemistry ; Coumaric Acids ; administration & dosage ; pharmacology ; Drug Carriers ; Humans ; Liposomes ; chemistry ; Membrane Potentials ; drug effects ; Mitochondria ; physiology ; Particle Size ; U937 Cells