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Mitochondrial Swelling (mitochondrial + swelling)
Selected AbstractsHistologic and morphologic effects of valproic acid and oxcarbazepine on rat uterine and ovarian cellsEPILEPSIA, Issue 1 2010Ali Cansu Summary Purpose:, To determine the histologic and morphologic effects of valproic acid (VPA) and oxcarbazepine (OXC) on rat uterine and ovarian cells. Methods:, Fifty-six female prepubertal Wistar rats (21,24 days old and weighing between 47.5 and 58.1 g) were divided equally into four groups, which were given drinking water (controls), 300 mg/kg/day of VPA, 100 mg/kg/day of OXC or VPA + OXC via gavage, for 90 days. Ovaries and uteri of rats on proestrous and diestrous phases of estrous cycle were extirpated and placed in a fixation solution. The tissue specimens were assessed with apoptosis (TUNEL) staining protocols, eosinophil counting, and electron microscopic techniques. Results:, In uteri, apoptosis in stroma, mitochondrial swelling, and cristolysis were observed in the VPA group, and OXC led to negative effects on epithelial cell and intracellular edema. In ovaries, both drugs increased apoptosis and intracytoplasmic edema. Organelle structure disruption was also observed in the OXC group. More conspicuous degenerative modifications were determined in the VPA + OXC group. In uteri, the number of TUNEL-positive luminal epithelial cells was 7.20 ± 1.32 in controls, and significantly increased to 29.60 ± 1.58, 34.20 ± 2.53, and 54.80 ± 2.04 in VPA, OXC, and VPA + OXC groups, respectively (p < 0.001). The highest number of TUNEL-positive glandular epithelium cells was observed in the VPA + OXC group; however, the number of TUNEL-positive stroma cells was highest in the VPA group. The highest number of eosinophils in stroma was in the VPA group. Conclusion:, VPA and OXC trigger apoptotic and degenerative effects on rat uterine and ovarian cells. VPA also prevents implantation of embryo to the uterus and causes abortion via endometrial eosinophil infiltration. [source] A folding variant of human ,-lactalbumin induces mitochondrial permeability transition in isolated mitochondriaFEBS JOURNAL, Issue 1 2001Camilla Köhler A human milk fraction containing multimeric ,-lactalbumin (MAL) is able to kill cells via apoptosis. MAL is a protein complex of a folding variant of ,-lactalbumin and lipids. Previous results have shown that upon treatment of transformed cells, MAL localizes to the mitochondria and cytochrome c is released into the cytosol. This is followed by activation of the caspase cascade. In this study, we further investigated the involvement of mitochondria in apoptosis induced by the folding variant of ,-lactalbumin. Addition of MAL to isolated rat liver mitochondria induced a loss of the mitochondrial membrane potential (,,m), mitochondrial swelling and the release of cytochrome c. These changes were Ca2+ -dependent and were prevented by cyclosporin A, an inhibitor of mitochondrial permeability transition. MAL also increased the rate of state 4 respiration in isolated mitochondria by exerting an uncoupling effect. This effect was due to the presence of fatty acids in the MAL complex because it was abolished completely by BSA. BSA delayed, but failed to prevent, mitochondrial swelling as well as dissipation of ,,m, indicating that the fatty acid content of MAL facilitated, rather than caused, these effects. Similar results were obtained with HAMLET (human ,-lactalbumin made lethal to tumour cells), which is native ,-lactalbumin converted in vitro to the apoptosis-inducing folding variant of the protein in complex with oleic acid. Our findings demonstrate that a folding variant of ,-lactalbumin induces mitochondrial permeability transition with subsequent cytochrome c release, which in transformed cells may lead to activation of the caspase cascade and apoptotic death. [source] Transepithelial elimination of cutaneous vulval granuloma inguinaleJOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2000Pratistadevi K. Ramdial Background: Transepithelial elimination (TEE), a distinct and well-known entity, is a process during which the skin eradicates undesirable or irritative dermal substances through intact epidermis or follicular epithelium by passive or active means. Although TEE is being described in an increasing number and range of pathological processes, to date, TEE of granuloma inguinale (GI) remains unrecorded in the English-language literature. The aims of this study were: 1) To appraise the light microscopic and ultrastructural morphological epidermal changes that are associated with TEE of cutaneous vulval GI; and 2) To determine the role of intra-epidermal leucocytes and histiocytes in the pathogenesis of TEE of vulval GI. Methods: This is a retrospective 9-year histopathological review of all cases diagnosed and coded as vulval granuloma inguinale in the Department of Anatomical Pathology, Nelson R. Mandela School of Medicine, University of Natal, Durban, South Africa. Ultrastructural evaluation was performed on selected cases using a Jeol transmission electron microscope. Results: Of 53 skin biopsies from 47 patients with vulval GI, 43 were suitable for the study. The age range of patients was 15,40 years (mean age=22 years). There were eleven papular, twelve nodular, seven verrucous and thirteen ulcerative lesions. Donovan bodies within macrophages, free-lying Donovan bodies and dense aggregates of neutrophils and plasma cells were seen in the dermis of all biopsies. There was consistent overlying pseudoepitheliomatous hyperplasia. The dermal inflammatory infiltrate hugged the dermo-epidermal junction and appeared entrapped between elongated and acanthotic epidermal rete ridges and pegs. Transepidermal neutrophil microabscesses, histiocytes containing Donovan bodies and neutrophilic and histiocytic fragmentation were present. A variable number of free-lying and intra-histiocytic Donovan bodies and neutrophils were present on the surface of the epidermis. On ultrastructural investigation epidermal spongiosis, intracellular oedema, free-lying, intra-neutrophilic and intra-histiocytic Donovan bodies, and intact and degenerating neutrophils and histiocytes were evident between keratinocytes. The degenerative histiocytes demonstrated marked vacuolation, mitochondrial swelling and bacilli within phagolysosomal vacuoles, bound by intact or disrupted limiting membranes. Conclusion: The inflammatory infiltrate at the epitheliomesenchymal interface, pseudoepitheliomatous hyperplasia, intra-epidermal accumulation and disintegration of neutrophils and histiocytes, and the associated release of lytic enzymes, play important contributory roles in TEE of GI. TEE of infectious agents is a poorly recognised mechanism of spread of infectious diseases and represents a public health hazard. In cutaneous vulval GI, TEE is highlighted as a hitherto unrecognised, potential method of spread of Calymmatobacterium granulomatis. [source] Calcium-induced Cytochrome c release from CNS mitochondria is associated with the permeability transition and rupture of the outer membraneJOURNAL OF NEUROCHEMISTRY, Issue 2 2002Nickolay Brustovetsky Abstract The mechanisms of Ca2+ -induced release of Cytochrome c (Cyt c) from rat brain mitochondria were examined quantitatively using a capture ELISA. In 75 or 125 mm KCl-based media 1.4 µmol Ca2+/mg protein caused depolarization and mitochondrial swelling. However, this resulted in partial Cyt c release only in 75 mm KCl. The release was inhibited by Ru360, an inhibitor of the Ca2+ uniporter, and by cyclosporin A plus ADP, a combination of mitochondrial permeability transition inhibitors. Transmission electron microscopy (TEM) revealed that Ca2+ -induced swelling caused rupture of the outer membrane only in 75 mm KCl. Koenig's polyanion, an inhibitor of mitochondrial porin (VDAC), enhanced swelling and amplified Cyt c release. Dextran T70 that is known to enhance mitochondrial contact site formation did not prevent Cyt c release. Exposure of cultured cortical neurons to 500 µm glutamate for 5 min caused Cyt c release into the cytosol 30 min after glutamate removal. MK-801 or CsA inhibited this release. Thus, the release of Cyt c from CNS mitochondria induced by Ca2+in vitro as well as in situ involved the mPT and appeared to require the rupture of the outer membrane. [source] Epidermal Growth Factor Induces Oxidative Neuronal Injury in Cortical CultureJOURNAL OF NEUROCHEMISTRY, Issue 1 2000Yoo Kyung Cha Abstract : Recently, we have demonstrated that certain neurotrophic factors can induce oxidative neuronal necrosis by acting at the cognate tyrosine kinase-linked receptors. Epidermal growth factor (EGF) has neurotrophic effects via the tyrosine kinase-linked EGF receptor (EGFR), but its neurotoxic potential has not been studied. Here, we examined this possibility in mouse cortical culture. Exposure of cortical cultures to 1-100 ng/ml EGF induced gradually developing neuronal death, which was complete in 48-72 h ; no injury to astrocytes was noted. Electron microscopic findings of EGF-induced neuronal death were consistent with necrosis ; severe mitochondrial swelling and disruption of cytoplasmic membrane occurred, whereas nuclei appeared relatively intact. The EGF-induced neuronal death was accompanied by increased free radical generation and blocked by the anti-oxidant Trolox. Suggesting mediation by the EGFR, an EGFR tyrosine kinase-specific inhibitor, C56, attenuated EGF-induced neuronal death. In addition, inhibitors of extracellular signal-regulated protein kinase 1/2 (Erk-1/2) (PD98056), protein kinase A (H89), and protein kinase C (GF109203X) blocked EGF-induced neuronal death. A p38 mitogen-activated protein kinase inhibitor (SB203580) or glutamate antagonists (MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione) showed no protective effect. The present results suggest that prolonged activation of the EGFR may trigger oxidative neuronal injury in central neurons. [source] Effect of amyloid ,-peptide on permeability transition pore: A comparative studyJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2002Paula I. Moreira Abstract A potentially central factor in neurodegeneration is the permeability transition pore (PTP). Because of the tissue-specific differences in pore properties, we directly compared isolated brain and liver mitochondria responses to the neurotoxic A, peptides. For this purpose, the following parameters were examined: mitochondrial membrane potential (,,m), respiration, swelling, ultrastructural morphology, and content of cytochrome c. Both peptides, A,25,35 (50 ,M) and A,1,40 (2 ,M), had a similar toxicity, exacerbating the effects of Ca2+, although, per se, they did not induce (PTP). In liver mitochondria, A, led to a drop in ,,m and potentiated matrix swelling and disruption induced by Ca2+. In contrast, brain mitochondria, exposed to the same conditions, demonstrated a higher capacity to accumulate Ca2+ before the ,,m drop and a slight increase of mitochondrial swelling compared with liver mitochondria. Furthermore, mitochondrial respiratory state 3 was depressed in the presence of A,, whereas state 4 was unaltered, resulting in an uncoupling of respiration. In both types of mitochondria, A, did not affect the content of cytochrome c. The ,,m drop was reversed when Ca2+ was removed by EGTA or when ADP plus oligomycin was present. Pretreatment with cyclosporin A or ADP plus oligomycin prevented the deleterious effects promoted by A, and/or Ca2+. It can be concluded that brain and liver mitochondria show a different susceptibility to the deleterious effect of A, peptide, brain mitochondria being more resistant to the potentiation by A, of Ca2+ -induced PTP. © 2002 Wiley-Liss, Inc. [source] Hepatoprotective activity of Terminalia catappa L. leaves and its two triterpenoidsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2004Jing Gao The aim of this study was to evaluate the effect of the chloroform extract of Terminalia catappa L. leaves (TCCE) on carbon tetrachloride (CCI4)-induced acute liver damage and D-galactosamine (D-GaIN)-induced hepatocyte injury. Moreover, the effects of ursolic acid and asiatic acid, two isolated components of TCCE, on mitochondria and free radicals were investigated to determine the mechanism underlying the action of TCCE on hepatotoxicity. In the acute hepatic damage test, remarkable rises in the activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (5.7- and 2.0-fold) induced by CCI4 were reversed and significant morphological changes were lessened with pre-treatment with 50 and 100 mg kg,1 TCCE. In the hepatocyte injury experiment, the increases in ALT and AST levels (1.9- and 2.1-fold) in the medium of primary cultured hepatocytes induced by D-GaIN were blocked by pre-treatment with 0.05, 0.1, 0.5 gL,1 TCCE. In addition, Ca2+ -induced mitochondrial swelling was dose-dependently inhibited by 50,500 ,m ursolic acid and asiatic acid. Both ursolic acid and asiatic acid, at concentrations ranging from 50 to 500 ,m, showed dose-dependent superoxide anion and hydroxyl radical scavenging activity. It can be concluded that TCCE has hepatoprotective activity and the mechanism is related to protection of liver mitochondria and the scavenging action on free radicals. [source] Cell death: regulation by the Bcl-2 protein familyPSYCHOGERIATRICS, Issue 2006Yoshihide TSUJIMOTO Abstract An increase in mitochondrial membrane permeability is central to cell death including apoptosis and necrosis. During apoptosis, permeabilization of outer mitochondrial membrane leads to the release of several apoptogenic factors, such as cytochrome c and Smac/Diablo, into the cytoplasm that activate downstream death programs, including apoptotic proteases called caspases, although the detailed mechanism of outer mitochondrial membrane permeabilization remains elusive. Although the mitochondrial membrane permeability transition (MPT), resulting in ,, loss, mitochondrial swelling and rupture of the outer membrane has initially been proposed as a general mechanism for apoptotic permeabilization of outer mitochondrial membrane, the recent studies with cyclophilin D-deficient mice indicate that MPT regulates some forms of necrotic death, but not apoptotic death, and that MPT is involved in ischemia,reperfusion injury in heart and brain. Anti-apoptotic proteins, Bcl-2 and Bcl-xL, efficiently block not only apoptotic mitochondrial permeabilization but also MPT. The present paper focuses on the mechanisms by which Bcl-2 family members control the permeability of mitochondrial membrane during apoptosis and necrosis. [source] Apoptosis in the Myocardium of the Adult Dromedary Camel: Ultrastructural CharacterizationANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 1 2010A.-H. K. Osman Summary Apoptosis is a highly regulated mode of cell death that occurs in the absence of inflammation. Light microscopic (LM) examination of the myocardium of apparently healthy camel did not reveal evidence of apoptosis in any samples; however, evidence of apoptosis was apparent by transmission electron microscopy (TEM). The most common apoptotic features observed by TEM included (1) an intact sarcolemma with some bleb formation; (2) nuclear chromatin condensation and margination with nucleolar disruption; (3) mitochondrial swelling and disorganization, accompanied by degeneration or hypercondensation of cristae; and (4) an intercalated disc region with a higher-than-normal mitochondrion/myofibril ratio, or surrounded from both sides by asymmetrically contracted sarcomeres. Apoptotic alterations were also noted among the endothelial cells lining the microvasculature of the myocardium. These alterations included (1) marked nuclear chromatin condensation and margination; (2) villous blebs on the adluminal plasmalemma, which projected into the lumen; (3) cytoplasmic vacuolation; (4) presence of intraluminal membrane-bounded vesicles; and (5) occasional pericapillary edema and accumulations of cellular debris. The results of this study indicate that myocardial apoptosis can occur in apparently healthy camels, in the absence of a clear-cut etiology. [source] Manganese alters mitochodrial integrity in the hearts of swine marginally deficient in magnesium,BIOFACTORS, Issue 2 2004Kevin B. Miller Abstract It was previously reported that pigs marginally deficient in magnesium (Mg) and fed diets high in manganese (Mn) died suddenly with signs of sudden cardiac death. Manganese, which has properties similar to Mg, may exacerbate Mg-deficiency and be accumulated by mitochondria resulting in ultrastructural damage. The objective of this study was to determine whether deaths of the type previously observed were mediated by adverse interactions of Mn and Mg resulting in ultrastructural damage to the myocardium, alterations in electrocardiographic recordings and tissue retention of Mn, Mg and calcium (Ca). Forty-eight pigs were fed one of six diets in a 2 × 3 factorial arrangement of Mg (100 or 1000 mg Mg/kg) and Mn (5, 50 or 500 mg Mn/kg) for 8 weeks. Left ventricle muscle samples were collected for examination by transmission electron microscopy. No differences in heart muscle ultrastructure were observed between pigs fed low and adequate dietary Mg. However, marked myocardial necrosis and mitochondrial swelling were observed in pigs fed high dietary Mn when combined with low Mg. Feeding low dietary Mg elevated minimum (P < 0.01), maximum (P < 0.05) and average (P < 0.001) heart rates. Low dietary Mg resulted in a 55% probability of a ventricular beat being recorded (P = 0.05) and lower Mg (P < 0.02) and Ca (P < 0.04) contents in heart atria and ventricles. These results suggest that high Mn, when fed in combination with low Mg, disrupts mitochondrial ultrastructure and is associated with the sudden deaths previously reported. [source] Malonate induces cell death via mitochondrial potential collapse and delayed swelling through an ROS-dependent pathwayBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2005Francisco J Fernandez-Gomez 1Herein we study the effects of the mitochondrial complex II inhibitor malonate on its primary target, the mitochondrion. 2Malonate induces mitochondrial potential collapse, mitochondrial swelling, cytochrome c (Cyt c) release and depletes glutathione (GSH) and nicotinamide adenine dinucleotide coenzyme (NAD(P)H) stores in brain-isolated mitochondria. 3Although, mitochondrial potential collapse was almost immediate after malonate addition, mitochondrial swelling was not evident before 15 min of drug presence. This latter effect was blocked by cyclosporin A (CSA), Ruthenium Red (RR), magnesium, catalase, GSH and vitamin E. 4Malonate added to SH-SY5Y cell cultures produced a marked loss of cell viability together with the release of Cyt c and depletion of GSH and NAD(P)H concentrations. All these effects were not apparent in SH-SY5Y cells overexpressing Bcl-xL. 5When GSH concentrations were lowered with buthionine sulphoximine, cytoprotection afforded by Bcl-xL overexpression was not evident anymore. 6Taken together, all these data suggest that malonate causes a rapid mitochondrial potential collapse and reactive oxygen species production that overwhelms mitochondrial antioxidant capacity and leads to mitochondrial swelling. Further permeability transition pore opening and the subsequent release of proapoptotic factors such as Cyt c could therefore be, at least in part, responsible for malonate-induced toxicity. British Journal of Pharmacology (2005) 144, 528,537. doi:10.1038/sj.bjp.0706069 [source] | |||||||||||||