scholarly journals Atypical Cristae Morphology of Human Syncytiotrophoblast Mitochondria

2011 ◽  
Vol 286 (27) ◽  
pp. 23911-23919 ◽  
Author(s):  
Daniela De Los Rios Castillo ◽  
Mariel Zarco-Zavala ◽  
Sofia Olvera-Sanchez ◽  
Juan Pablo Pardo ◽  
Oscar Juarez ◽  
...  

Mitochondrial complexes I, III2, and IV from human cytotrophoblast and syncytiotrophoblast associate to form supercomplexes or respirasomes, with the following stoichiometries: I1:(III2)1 and I1:(III2)1–2:IV1–4. The content of respirasomes was similar in both cell types after isolating mitochondria. However, syncytiotrophoblast mitochondria possess low levels of dimeric complex V and do not have orthodox cristae morphology. In contrast, cytotrophoblast mitochondria show normal cristae morphology and a higher content of ATP synthase dimer. Consistent with the dimerizing role of the ATPase inhibitory protein (IF1) (García, J. J., Morales-Ríos, E., Cortés-Hernandez, P., and Rodríguez-Zavala, J. S. (2006) Biochemistry 45, 12695–12703), higher relative amounts of IF1 were observed in cytotrophoblast when compared with syncytiotrophoblast mitochondria. Therefore, there is a correlation between dimerization of complex V, IF1 expression, and the morphology of mitochondrial cristae in human placental mitochondria. The possible relationship between cristae architecture and the physiological function of the syncytiotrophoblast mitochondria is discussed.

2021 ◽  
Vol 22 (14) ◽  
pp. 7360
Author(s):  
Angie De La Cruz ◽  
Aubrey Hargrave ◽  
Sri Magadi ◽  
Justin A. Courson ◽  
Paul T. Landry ◽  
...  

Platelet extravasation during inflammation is under-appreciated. In wild-type (WT) mice, a central corneal epithelial abrasion initiates neutrophil (PMN) and platelet extravasation from peripheral limbal venules. The same injury in mice expressing low levels of the β2-integrin, CD18 (CD18hypo mice) shows reduced platelet extravasation with PMN extravasation apparently unaffected. To better define the role of CD18 on platelet extravasation, we focused on two relevant cell types expressing CD18: PMNs and mast cells. Following corneal abrasion in WT mice, we observed not only extravasated PMNs and platelets but also extravasated erythrocytes (RBCs). Ultrastructural observations of engorged limbal venules showed platelets and RBCs passing through endothelial pores. In contrast, injured CD18hypo mice showed significantly less venule engorgement and markedly reduced platelet and RBC extravasation; mast cell degranulation was also reduced compared to WT mice. Corneal abrasion in mast cell-deficient (KitW-sh/W-sh) mice showed less venule engorgement, delayed PMN extravasation, reduced platelet and RBC extravasation and delayed wound healing compared to WT mice. Finally, antibody-induced depletion of circulating PMNs prior to corneal abrasion reduced mast cell degranulation, venule engorgement, and extravasation of PMNs, platelets, and RBCs. In summary, in the injured cornea, platelet and RBC extravasation depends on CD18, PMNs, and mast cell degranulation.


Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2628-2631 ◽  
Author(s):  
Martin Leverkus ◽  
Henning Walczak ◽  
Alex McLellan ◽  
Hans-Werner Fries ◽  
Gabi Terbeck ◽  
...  

Dendritic cells (DCs) disappear from lymph nodes 1 to 2 days after antigen presentation, presumably by apoptosis. To evaluate the role of death ligands in elimination of DCs, we analyzed the sensitivity of human DCs to CD95 ligand (CD95L) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We found mature DCs to be resistant to killing via CD95L or TRAIL, whereas only immature DCs were partially sensitive. However, all DC populations expressed CD95, TRAIL-R2, and TRAIL-R3 at comparable levels, suggesting that sensitivity to death ligand-induced DC apoptosis is not regulated at the receptor level. Interestingly, mature DCs highly expressed the caspase 8 inhibitory protein cFLIP, whereas only low levels were detected in immature DCs. Thus, death ligand sensitivity proved to be dependent on DC maturation and inversely correlated with expression levels of cFLIP. Induction of apoptosis by TRAIL or CD95L does not seem to play a role in the elimination of mature DCs, but instead might serve to regulate immature DC populations.


2022 ◽  
Vol 13 (1) ◽  
pp. 1-2
Author(s):  
Karthikeyan Pethusamy ◽  
Ruby Dhar ◽  
Arun Kumar ◽  
Subhradip Karmakar

Cell to Cell communications is the pivot for life processes. Any event that disrupts this leads to the loss of physiological function, eventually leading to cell death. Evolutionarily, cells developed an elaborate mechanism to undertake this paramount responsibility through cell surface glycocalyx, receptors, integrins, and other recognition molecules. Cells also exchange through local acting soluble mediators as well as through vesicles and exosomes. Recent development in this field led to the identification of a spectacular network of membrane process that seems to be the supremo of all that was known about cellular communications. These are called membrane nanotubes or tunneling nanotubes (TNT). Cellular communication can be subdivided into contact and contactless. The former provides more rapid and molecule transfer as compared to the latter. Tunneling nanotubes (TNTs) are a novel type of contact-based communication. TNTs are straight, thin membrane extensions connecting cells over long distances first reported in PC12 cells in 2004. TNT is believed to form from actin-based membrane protrusion. There are three different models of TNT formation. a>Protrusions from one cell grow and extend until it reaches the other cell, followed by a membrane fusion. b> Membrane protrusions grow from both cells until they meet and establish a connection c> TNT formation by cell dislodgement when cells migrate further apart from each other, and during this movement, TNT is formed. It is possible that all these three models may be operational depending on cell types and context. Tunneling nanotubes (TNT) are dynamic connections between cells, representing a novel route for cell-to-cell communication. TNT was reported in various cell types, like epithelial cells, neuronal cells, mesenchyma cells, and immune cells engaged in intercellular exchanges of molecules, subcellular organelles, and pathogen and viruses transport routes. TNT can extend up to 200 µm in length and about 50 nm to 1500 nm in diameter in macrophages. TNT can be established between similar cell types (homo-TNT) or between one cell type and another ( hetro TNT) and thus may be involved in the initiation and growth of cancer as well as dissemination of cancer cells. TNTs are also assumed to play a role in treatment resistance, e.g., in chemotherapy treatment of cancer. Recently, TNT has been used to hijack mitochondria from healthy cells by the cancer cells as a source of energy. TNT was also reported to transport miRNA and other RNA to the surrounding stroma creating an environment suitable for cancer growth. More research in this discipline is needed to understand the full function of these wonderful nanostructures.


1994 ◽  
Vol 14 (6) ◽  
pp. 3906-3914 ◽  
Author(s):  
J S Crosby ◽  
K Lee ◽  
I M London ◽  
J J Chen

The role of heme-regulated eIF-2 alpha kinase (HRI) in the regulation of protein synthesis in rabbit reticulocytes is well documented. Inhibitors of protein synthesis with properties similar to those of HRI have been described in some nonerythroid cell types, but it has not yet been determined whether these eIF-2 alpha kinase activities are mediated by HRI or one or more as yet uncharacterized kinases. We have studied the expression of mRNA, polypeptide, and kinase activities of HRI in various tissues from both nonanemic and anemic rabbits. Our results indicate that HRI is expressed in an erythroid cell-specific manner. HRI is present in the bone marrow and peripheral blood of both nonanemic and anemic rabbits but not in any of the other tissues tested. HRI mRNA is present at low levels in uninduced mouse erythroleukemic (MEL) cells and human K562 cells and accumulates to higher levels upon induction. The accumulation of HRI mRNA in differentiating MEL cells is dependent upon the presence of heme. The addition of 3-amino-1,2,4-triazole (AT), an inhibitor of heme biosynthesis, to the induction medium markedly reduced HRI mRNA accumulation. Simultaneous addition of hemin and AT to the dimethyl sulfoxide induction medium largely prevented the inhibition of HRI mRNA induction by AT. These findings indicate that HRI is expressed in an erythroid cell-specific manner and that the major physiologic role of HRI is in adjusting the synthesis of globins to the availability of heme.


1994 ◽  
Vol 14 (6) ◽  
pp. 3906-3914
Author(s):  
J S Crosby ◽  
K Lee ◽  
I M London ◽  
J J Chen

The role of heme-regulated eIF-2 alpha kinase (HRI) in the regulation of protein synthesis in rabbit reticulocytes is well documented. Inhibitors of protein synthesis with properties similar to those of HRI have been described in some nonerythroid cell types, but it has not yet been determined whether these eIF-2 alpha kinase activities are mediated by HRI or one or more as yet uncharacterized kinases. We have studied the expression of mRNA, polypeptide, and kinase activities of HRI in various tissues from both nonanemic and anemic rabbits. Our results indicate that HRI is expressed in an erythroid cell-specific manner. HRI is present in the bone marrow and peripheral blood of both nonanemic and anemic rabbits but not in any of the other tissues tested. HRI mRNA is present at low levels in uninduced mouse erythroleukemic (MEL) cells and human K562 cells and accumulates to higher levels upon induction. The accumulation of HRI mRNA in differentiating MEL cells is dependent upon the presence of heme. The addition of 3-amino-1,2,4-triazole (AT), an inhibitor of heme biosynthesis, to the induction medium markedly reduced HRI mRNA accumulation. Simultaneous addition of hemin and AT to the dimethyl sulfoxide induction medium largely prevented the inhibition of HRI mRNA induction by AT. These findings indicate that HRI is expressed in an erythroid cell-specific manner and that the major physiologic role of HRI is in adjusting the synthesis of globins to the availability of heme.


2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Kristen Leslie ◽  
GyunJee Song ◽  
Stacey Barrick ◽  
Alessandro Bisello

Inflammation plays a fundamental role in the development of cardiovascular diseases such as atherosclerosis and restenosis. The vascular response to inflammation in these diseases requires communication between multiple cell types such as vascular smooth muscle cells (VSMC) and macrophages. We have identified a scaffolding protein, Ezrin Binding Protein 50 (EBP50, also known as NHERF-1), which is expressed at very low levels in normal vessels but is up-regulated following vascular injury. EBP50 promotes VSMC proliferation and neointima formation after wire injury in mouse femoral arteries. In the current study, we hypothesized that EBP50 functions as a central mediator linking macrophage activation and the response of vessels to inflammation. Similar to the observations in vessels, treatment of primary VSMC and macrophages with LPS or TNFα increased EBP50 expression. This increase was dependent on NF-κB signaling because pharmacological inhibition of NF-κB and expression of a dominant negative IκBα abolished the induction of EBP50. Interestingly, LPS-induced activation of NF-κB (determined by phosphorylation of IKKα/β, degradation of IκBα, and p65 phosphorylation) was impaired in EBP50 null VSMC and macrophages. Moreover, nuclear translocation of the p65 subunit of NF-κB was also reduced in EBP50 -/- VSMC. Consistent with the role of EBP50 on NF-κB, LPS- and TNFα-induced macrophage activation (determined by the expression of the inflammatory markers iNOS, TNFα, and IL-1β) was reduced in EBP50 -/- macrophages and mice. Similarly, the expression of iNOS, VCAM-1, and ICAM-1 in VSMC was decreased in EBP50 -/- VSMC and mice. Collectively, these observations indicate that EBP50 and NF-κB participate in a positive feedback loop leading to increased macrophage activation and enhanced response of VSMC to inflammation, suggesting its involvement in vascular remodeling.


2015 ◽  
Vol 54 (2) ◽  
pp. R103-R117 ◽  
Author(s):  
Talitha van der Meulen ◽  
Mark O Huising

The α and β cells act in concert to maintain blood glucose. The α cells release glucagon in response to low levels of glucose to stimulate glycogenolysis in the liver. In contrast, β cells release insulin in response to elevated levels of glucose to stimulate peripheral glucose disposal. Despite these opposing roles in glucose homeostasis, α and β cells are derived from a common progenitor and share many proteins important for glucose sensing and hormone secretion. Results from recent work have underlined these similarities between the two cell types by revealing that β-to-α as well as α-to-β transdifferentiation can take place under certain experimental circumstances. These exciting findings highlight unexpected plasticity of adult islets and offer hope of novel therapeutic paths to replenish β cells in diabetes. In this review, we focus on the transcription factor networks that establish and maintain pancreatic endocrine cell identity and how they may be perturbed to facilitate transdifferentiation.


Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2628-2631 ◽  
Author(s):  
Martin Leverkus ◽  
Henning Walczak ◽  
Alex McLellan ◽  
Hans-Werner Fries ◽  
Gabi Terbeck ◽  
...  

Abstract Dendritic cells (DCs) disappear from lymph nodes 1 to 2 days after antigen presentation, presumably by apoptosis. To evaluate the role of death ligands in elimination of DCs, we analyzed the sensitivity of human DCs to CD95 ligand (CD95L) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We found mature DCs to be resistant to killing via CD95L or TRAIL, whereas only immature DCs were partially sensitive. However, all DC populations expressed CD95, TRAIL-R2, and TRAIL-R3 at comparable levels, suggesting that sensitivity to death ligand-induced DC apoptosis is not regulated at the receptor level. Interestingly, mature DCs highly expressed the caspase 8 inhibitory protein cFLIP, whereas only low levels were detected in immature DCs. Thus, death ligand sensitivity proved to be dependent on DC maturation and inversely correlated with expression levels of cFLIP. Induction of apoptosis by TRAIL or CD95L does not seem to play a role in the elimination of mature DCs, but instead might serve to regulate immature DC populations.


Author(s):  
W.T. Gunning ◽  
M.R. Marino ◽  
M.S. Babcock ◽  
G.D. Stoner

The role of calcium in modulating cellular replication and differentiation has been described for various cell types. In the present study, the effects of Ca++ on the growth and differentiation of cultured rat esophageal epithelial cells was investigated.Epithelial cells were isolated from esophagi taken from 8 week-old male CDF rats by the enzymatic dissociation method of Kaighn. The cells were cultured in PFMR-4 medium supplemented with 0.25 mg/ml dialyzed fetal bovine serum, 5 ng/ml epidermal growth factor, 10-6 M hydrocortisone 10-6 M phosphoethanolamine, 10-6 M ethanolamine, 5 pg/ml insulin, 5 ng/ml transferrin, 10 ng/ml cholera toxin and 50 ng/ml garamycin at 36.5°C in a humidified atmosphere of 3% CO2 in air. At weekly intervals, the cells were subcultured with a solution containing 1% polyvinylpyrrolidone, 0.01% EGTA, and 0.05% trypsin. After various passages, the replication rate of the cells in PFMR-4 medium containing from 10-6 M to 10-3 M Ca++ was determined using a clonal growth assay.


Author(s):  
A.J. Mia ◽  
L.X. Oakford ◽  
T. Yorio

Protein kinase C (PKC) isozymes, when activated, are translocated to particulate membrane fractions for transport to the apical membrane surface in a variety of cell types. Evidence of PKC translocation was demonstrated in human megakaryoblastic leukemic cells, and in cardiac myocytes and fibroblasts, using FTTC immunofluorescent antibody labeling techniques. Recently, we reported immunogold localizations of PKC subtypes I and II in toad urinary bladder epithelia, following 60 min stimulation with Mezerein (MZ), a PKC activator, or antidiuretic hormone (ADH). Localization of isozyme subtypes I and n was carried out in separate grids using specific monoclonal antibodies with subsequent labeling with 20nm protein A-gold probes. Each PKC subtype was found to be distributed singularly and in discrete isolated patches in the cytosol as well as in the apical membrane domains. To determine if the PKC isozymes co-localized within the cell, a double immunogold labeling technique using single grids was utilized.


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