scholarly journals Antiaging Properties of a Grape-Derived Antioxidant Are Regulated by Mitochondrial Balance of Fusion and Fission Leading to Mitophagy Triggered by a Signaling Network of Sirt1-Sirt3-Foxo3-PINK1-PARKIN

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Somak Das ◽  
Goran Mitrovsky ◽  
Hannah R. Vasanthi ◽  
Dipak K. Das
Keyword(s):  
Electron Microscopy ◽  
Signal Transduction ◽  
Transmission Electron Microscopy ◽  
Confocal Microscopy ◽  
Mitochondrial Fission ◽  
Signal Transduction Cascade ◽  
Original Proposal ◽  
Transmission Electron ◽  
Rat Hearts ◽  
Intracellular Glutathione

It was proposed that resveratrol, a polyphenolic antioxidant and a calorie restriction mimetic could promote longevity but subsequent studies could not prove this. The original proposal was based on the fact that a grape-derived antioxidant could activate the antiaging gene Sirt1. Most studies agree that indeed grape activates Sirt1, but a question remains whether Sirt1 is the cause or consequence of resveratrol treatment. Subsequently, mitochondrial Sirt3 was found to be activated. The present study on ischemic reperfusion (I/R) in rat hearts demonstrates that Foxo3a is activated subsequent to Sirt3 activation, which then activates PINK1. PINK1 potentiates activation of PARKIN leading to the activation of mitochondrial fission and mitophagy. Confocal microscopy conclusively shows the coexistence of Sirt3 with Foxo3a and Foxo3a with PINK1 and PARKIN. Mitophagy was demonstrated both by confocal microscopy and transmission electron microscopy. Western blot analyses data are consistent with the results of confocal microscopy. It appears that the grape-derived antioxidant modifies the intracellular environment by changing the oxidizing milieu into a reducing milieu and upregulating intracellular glutathione, potentiates a signal transduction cascade consisting of Sirt1/Sirt3-Foxo3a-PINK1-PARKIN-mitochondrial fusion fission-mitophagy that leads to cardioprotection, and paves the way to an anti-aging environment.

scholarly journals Protective Effects of Anti-depressant Citalopram Against Abnormal APP Processing and Amyloid Beta-induced Mitochondrial Dynamics, Biogenesis, Mitophagy and Synaptic Toxicities in Alzheimer’s Disease

2021 ◽  
Author(s):  
Arubala P Reddy ◽  
Xiangling Yin ◽  
Neha Sawant ◽  
P Hemachandra Reddy
Keyword(s):  
Electron Microscopy ◽  
Alzheimer’S Disease ◽  
Transmission Electron Microscopy ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Protective Role ◽  
Mrna Levels ◽  
Ht22 Cells ◽  
Transmission Electron

Abstract The purpose of this study is to study the neuroprotective role of selective serotonin reuptake inhibitor (SSRI), citalopram against Alzheimer’s disease (ad). Multiple SSRIs, including citalopram are reported to treat patients with depression, anxiety, and ad. However, their protective cellular mechanisms have not been studied completely. In the current study, we investigated the protective role of citalopram against impaired mitochondrial dynamics, defective mitochondrial biogenesis, defective mitophagy, and synaptic dysfunction in immortalized mouse primary hippocampal cells (HT22) expressing mutant APP (SWI/IND) mutations. Using quantitative RT-PCR, immunoblotting, biochemical methods and transmission electron microscopy methods, we assessed mutant full-length APP/C-terminal fragments and Aβ levels and mRNA and protein levels of mitochondrial dynamics, biogenesis, mitophagy, and synaptic genes in mAPP-HT22 cells and mAPP-HT22 cells treated with citalopram. Increased levels of mRNA levels of mitochondrial fission genes, decreased levels of fusion biogenesis, autophagy, mitophagy and synaptic genes were found in mAPP-HT22 cells relative to WT-HT22 cells. However, in mAPP-HT22 cells treated with citalopram compared to mAPP-HT22 cells, revealed reduced levels of the mitochondrial fission genes, increased fusion, biogenesis, autophagy, mitophagy, and synaptic genes. Our protein data agrees with mRNA levels. Transmission electron microscopy revealed significantly increased mitochondrial numbers and reduced mitochondrial length in mAPP-HT22 cells; these were reversed in citalopram treated mAPP-HT22 cells. Cell survival rates were increased in citalopram treated mAPP-HT22 relative to citalopram-untreated mAPP-HT22. Further, mAPP and C-terminal fragments were also reduced in citalopram treated cells. These findings suggest that citalopram reduces mutant APP and Aβ and mitochondrial toxicities and may have a protective role of mutant APP and Aβ-induced injuries in patients with depression, anxiety, and ad.

Endocytic pathway of exogenous iron-loaded ferritin in intestinal epithelial (Caco-2) cells

2013 ◽  
Vol 304 (7) ◽  
pp. G655-G661 ◽  
Author(s):  
Elmer Antileo ◽  
Carolina Garri ◽  
Victoria Tapia ◽  
Juan Pablo Muñoz ◽  
Mario Chiong ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Confocal Microscopy ◽  
Apical Membrane ◽  
Heme Iron ◽  
Endocytic Pathway ◽  
Coated Pits ◽  
Fluorescence Confocal Microscopy ◽  
Transmission Electron ◽  
Early Endosomes

Ferritin, a food constituent of animal and vegetal origin, is a source of dietary iron. Its hollow central cavity has the capacity to store up to 4,500 atoms of iron, so its potential as an iron donor is advantageous to heme iron, present in animal meats and inorganic iron of mineral or vegetal origin. In intestinal cells, ferritin internalization by endocytosis results in the release of its iron into the cytosolic labile iron pool. The aim of this study was to characterize the endocytic pathway of exogenous ferritin absorbed from the apical membrane of intestinal epithelium Caco-2 cells, using both transmission electron microscopy and fluorescence confocal microscopy. Confocal microscopy revealed that endocytosis of exogenous AlexaFluor 488-labeled ferritin was initiated by its engulfment by clathrin-coated pits and internalization into early endosomes, as determined by codistribution with clathrin and early endosome antigen 1 (EEA1). AlexaFluor 488-labeled ferritin also codistributed with the autophagosome marker microtubule-associated protein 1 light chain 3 (LC3) and the lysosome marker lysosomal-associated membrane protein 2 (LAMP2). Transmission electron microscopy revealed that exogenously added ferritin was captured in plasmalemmal pits, double-membrane compartments, and multivesicular bodies considered as autophagosomes and lysosomes. Biochemical experiments revealed that the lysosome inhibitor chloroquine and the autophagosome inhibitor 3-methyladenine (3-MA) inhibited degradation of exogenously added 131I-labeled ferritin. This evidence is consistent with a model in which exogenous ferritin is internalized from the apical membrane through clathrin-coated pits, and then follows a degradation pathway consisting of the passage through early endosomes, autophagosomes, and autolysosomes.

Techniques for Transmission Electron Microscopy of Fiber-Matrix Interfaces in Aluminum Alloy-Boron Composites by Ion Erosio

1971 ◽  
Vol 29 ◽  
pp. 204-205
Author(s):  
G. G. Shaw
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Aluminum Alloy ◽  
Electron Beam ◽  
Pure Aluminum ◽  
Ion Milling ◽  
Transmission Electron ◽  
Fiber Matrix ◽  
Ion Erosion ◽  
Row Of Fibers

The morphology and composition of the fiber-matrix interface can best be studied by transmission electron microscopy and electron diffraction. For some composites satisfactory samples can be prepared by electropolishing. For others such as aluminum alloy-boron composites ion erosion is necessary.When one wishes to examine a specimen with the electron beam perpendicular to the fiber, preparation is as follows: A 1/8 in. disk is cut from the sample with a cylindrical tool by spark machining. Thin slices, 5 mils thick, containing one row of fibers, are then, spark-machined from the disk. After spark machining, the slice is carefully polished with diamond paste until the row of fibers is exposed on each side, as shown in Figure 1.In the case where examination is desired with the electron beam parallel to the fiber, preparation is as follows: Experimental composites are usually 50 mils or less in thickness so an auxiliary holder is necessary during ion milling and for easy transfer to the electron microscope. This holder is pure aluminum sheet, 3 mils thick.

Direct Observation of Heat Exchanger Deposits by Cross Sectioning

1967 ◽  
Vol 25 ◽  
pp. 364-365
Author(s):  
R. W. Anderson ◽  
D. L. Senecal
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Heat Exchanger ◽  
Direct Observation ◽  
Cross Sections ◽  
Preparation Method ◽  
Specimen Preparation ◽  
Flowing Water ◽  
Transmission Electron ◽  
Deposit Layer

A problem was presented to observe the packing densities of deposits of sub-micron corrosion product particles. The deposits were 5-100 mils thick and had formed on the inside surfaces of 3/8 inch diameter Zircaloy-2 heat exchanger tubes. The particles were iron oxides deposited from flowing water and consequently were only weakly bonded. Particular care was required during handling to preserve the original formations of the deposits. The specimen preparation method described below allowed direct observation of cross sections of the deposit layers by transmission electron microscopy.The specimens were short sections of the tubes (about 3 inches long) that were carefully cut from the systems. The insides of the tube sections were first coated with a thin layer of a fluid epoxy resin by dipping. This coating served to impregnate the deposit layer as well as to protect the layer if subsequent handling were required.

Phase Transformations in Ti-7w/oMo-3w/oMe Alloy

1974 ◽  
Vol 32 ◽  
pp. 514-515
Author(s):  
S. Fujishiro
Keyword(s):  
Electron Microscopy ◽  
Mechanical Properties ◽  
Transmission Electron Microscopy ◽  
Tensile Strength ◽  
Mechanical Processing ◽  
Ray Method ◽  
X Ray ◽  
Transmission Electron ◽  
Water Quench ◽  
Alpha Beta

The mechanical properties of three titanium alloys (Ti-7Mo-3Al, Ti-7Mo- 3Cu and Ti-7Mo-3Ta) were evaluated as function of: 1) Solutionizing in the beta field and aging, 2) Thermal Mechanical Processing in the beta field and aging, 3) Solutionizing in the alpha + beta field and aging. The samples were isothermally aged in the temperature range 300° to 700*C for 4 to 24 hours, followed by a water quench. Transmission electron microscopy and X-ray method were used to identify the phase formed. All three alloys solutionized at 1050°C (beta field) transformed to martensitic alpha (alpha prime) upon being water quenched. Despite this heavily strained alpha prime, which is characterized by microtwins the tensile strength of the as-quenched alloys is relatively low and the elongation is as high as 30%.

Two- or three-way observations of the identical cell elements within the same sections by LM, TEM and/or SEM

1978 ◽  
Vol 36 (2) ◽  
pp. 82-83 ◽  
Author(s):  
Nakazo Watari ◽  
Yasuaki Hotta ◽  
Yoshio Mabuchi
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Fine Structure ◽  
Light Microscopy ◽  
Thin Sections ◽  
Transmission Electron ◽  
Identical Cell ◽  
Electron Microscopes ◽  
Scanning Electron

It is very useful if we can observe the identical cell elements within the same sections by light microscopy (LM), transmission electron microscopy (TEM) and/or scanning electron microscopy (SEM) sequentially, because, the cell fine structure can not be indicated by LM, while the color is; on the other hand, the cell fine structure can be very easily observed by EM, although its color properties may not. However, there is one problem in that LM requires thick sections of over 1 μm, while EM needs very thin sections of under 100 nm. Recently, we have developed a new method to observe the same cell elements within the same plastic sections using both light and transmission (conventional or high-voltage) electron microscopes.In this paper, we have developed two new observation methods for the identical cell elements within the same sections, both plastic-embedded and paraffin-embedded, using light microscopy, transmission electron microscopy and/or scanning electron microscopy (Fig. 1).

Comparative Microstructures of Ion Milled and Electrochemically Thinned Composite Materials

1974 ◽  
Vol 32 ◽  
pp. 546-547
Author(s):  
R.R. Russell
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Composite Materials ◽  
Great Difficulty ◽  
Ion Milling ◽  
Transmission Electron ◽  
Ion Damage ◽  
Intermetallic Composite

Transmission electron microscopy of metallic/intermetallic composite materials is most challenging since the microscopist typically has great difficulty preparing specimens with uniform electron thin areas in adjacent phases. The application of ion milling for thinning foils from such materials has been quite effective. Although composite specimens prepared by ion milling have yielded much microstructural information, this technique has some inherent drawbacks such as the possible generation of ion damage near sample surfaces.

Maytansine-Induced Mitotic Arrest in Human Lymphoblasts

1977 ◽  
Vol 35 ◽  
pp. 460-461
Author(s):  
Tai-Te Chao ◽  
John Sullivan ◽  
Awtar Krishan
Keyword(s):  
Electron Microscopy ◽  
Cell Cycle ◽  
Transmission Electron Microscopy ◽  
Tubulin Polymerization ◽  
Vinca Alkaloids ◽  
Antimitotic Activity ◽  
Transmission Electron ◽  
Flow Microfluorometry ◽  
Brain Tubulin

Maytansine, a novel ansa macrolide (1), has potent anti-tumor and antimitotic activity (2, 3). It blocks cell cycle traverse in mitosis with resultant accumulation of metaphase cells (4). Inhibition of brain tubulin polymerization in vitro by maytansine has also been reported (3). The C-mitotic effect of this drug is similar to that of the well known Vinca- alkaloids, vinblastine and vincristine. This study was carried out to examine the effects of maytansine on the cell cycle traverse and the fine struc- I ture of human lymphoblasts.Log-phase cultures of CCRF-CEM human lymphoblasts were exposed to maytansine concentrations from 10-6 M to 10-10 M for 18 hrs. Aliquots of cells were removed for cell cycle analysis by flow microfluorometry (FMF) (5) and also processed for transmission electron microscopy (TEM). FMF analysis of cells treated with 10-8 M maytansine showed a reduction in the number of G1 cells and a corresponding build-up of cells with G2/M DNA content.

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