Differential role of presenilin-1 and -2 on mitochondrial membrane potential and oxygen consumption in mouse embryonic fibroblasts

2006 ◽  
Vol 84 (4) ◽  
pp. 891-902 ◽  
Author(s):  
Homira Behbahani ◽  
Irina G. Shabalina ◽  
Birgitta Wiehager ◽  
Hérnan Concha ◽  
Kjell Hultenby ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Presenilin 1 ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts

Modulation of neuronal mitochondrial membrane potential by the NMDA receptor: role of arachidonic acid

1997 ◽  
Vol 777 (1-2) ◽  
pp. 69-74 ◽  
Author(s):  
Antonio Camins ◽  
Francesc X Sureda ◽  
Cecilia Gabriel ◽  
Mercè Pallàs ◽  
Elena Escubedo ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Membrane Potential ◽  
Nmda Receptor ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane

The role of mitochondrial membrane potential in ischemic heart failure

Mitochondrion ◽  
2011 ◽  
Vol 11 (5) ◽  
pp. 700-706 ◽  
Author(s):  
Bernhard Kadenbach ◽  
Rabia Ramzan ◽  
Rainer Moosdorf ◽  
Sebastian Vogt
Keyword(s):  
Heart Failure ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Ischemic Heart ◽  
Ischemic Heart Failure

scholarly journals Mitochondrial dysfunction in insulin resistance: differential contributions of chronic insulin and saturated fatty acid exposure in muscle cells

2012 ◽  
Vol 32 (5) ◽  
pp. 465-478 ◽  
Author(s):  
Chenjing Yang ◽  
Cho Cho Aye ◽  
Xiaoxin Li ◽  
Angels Diaz Ramos ◽  
Antonio Zorzano ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Oxygen Consumption ◽  
Fatty Acid ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Saturated Fatty Acid ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Acid Exposure ◽  
High Insulin

Mitochondrial dysfunction has been associated with insulin resistance, obesity and diabetes. Hyperinsulinaemia and hyperlipidaemia are hallmarks of the insulin-resistant state. We sought to determine the contributions of high insulin and saturated fatty acid exposure to mitochondrial function and biogenesis in cultured myocytes. Differentiated C2C12 myotubes were left untreated or exposed to chronic high insulin or high palmitate. Mitochondrial function was determined assessing: oxygen consumption, mitochondrial membrane potential, ATP content and ROS (reactive oxygen species) production. We also determined the expression of several mitochondrial genes. Chronic insulin treatment of myotubes caused insulin resistance with reduced PI3K (phosphoinositide 3-kinase) and ERK (extracellular-signal-regulated kinase) signalling. Insulin treatment increased oxygen consumption but reduced mitochondrial membrane potential and ROS production. ATP cellular levels were maintained through an increased glycolytic rate. The expression of mitochondrial OXPHOS (oxidative phosphorylation) subunits or Mfn-2 (mitofusin 2) were not significantly altered in comparison with untreated cells, whereas expression of PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α) and UCPs (uncoupling proteins) were reduced. In contrast, saturated fatty acid exposure caused insulin resistance, reducing PI3K (phosphoinositide 3-kinase) and ERK (extracellular-signal-regulated kinase) activation while increasing activation of stress kinases JNK (c-Jun N-terminal kinase) and p38. Fatty acids reduced oxygen consumption and mitochondrial membrane potential while up-regulating the expression of mitochondrial ETC (electron chain complex) protein subunits and UCP proteins. Mfn-2 expression was not modified by palmitate. Palmitate-treated cells also showed a reduced glycolytic rate. Taken together, our findings indicate that chronic insulin and fatty acid-induced insulin resistance differentially affect mitochondrial function. In both conditions, cells were able to maintain ATP levels despite the loss of membrane potential; however, different protein expression suggests different adaptation mechanisms.

scholarly journals 2P243 The role of cyclophilin D on persistence of mitochondrial membrane potential

2004 ◽  
Vol 44 (supplement) ◽  
pp. S170
Author(s):  
H. Suzuki ◽  
K. Machida ◽  
K. Higashino ◽  
C. Fujita ◽  
H. Osada ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Cyclophilin D

scholarly journals The Interferon Stimulator Mitochondrial Antiviral Signaling Protein Facilitates Cell Death by Disrupting the Mitochondrial Membrane Potential and by Activating Caspases

2009 ◽  
Vol 84 (5) ◽  
pp. 2421-2431 ◽  
Author(s):  
Chia-Yi Yu ◽  
Ruei-Lin Chiang ◽  
Tsung-Hsien Chang ◽  
Ching-Len Liao ◽  
Yi-Ling Lin
Keyword(s):  
Cell Death ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Caspase Cleavage ◽  
Infected Cells ◽  
Mitochondrial Antiviral Signaling ◽  
Antiviral Innate Immunity ◽  
Viral Components

ABSTRACT Interferon (IFN) signaling is initiated by the recognition of viral components by host pattern recognition receptors. Dengue virus (DEN) triggers IFN-β induction through a molecular mechanism involving the cellular RIG-I/MAVS signaling pathway. Here we report that the MAVS protein level is reduced in DEN-infected cells and that caspase-1 and caspase-3 cleave MAVS at residue D429. In addition to its well-known function in IFN induction, MAVS is also a proapoptotic molecule that triggers disruption of the mitochondrial membrane potential and activation of caspases. Although different domains are required for the induction of cytotoxicity and IFN, caspase cleavage at residue 429 abolished both functions of MAVS. The apoptotic role of MAVS in viral infection and double-stranded RNA (dsRNA) stimulation was demonstrated in cells with reduced endogenous MAVS expression induced by RNA interference. Even though IFN-β promoter activation was largely suppressed, DEN production was not affected greatly in MAVS knockdown cells. Instead, DEN- and dsRNA-induced cell death and caspase activation were delayed and attenuated in the cells with reduced levels of MAVS. These results reveal a new role of MAVS in the regulation of cell death beyond its well-known function of IFN induction in antiviral innate immunity.

scholarly journals EPAC1 Inhibition Protects the Heart from Doxorubicin-Induced Toxicity

2021 ◽  
Author(s):  
Marianne Mazevet ◽  
Maxance Ribeiro ◽  
Anissa Belhadef ◽  
Delphine Dayde ◽  
Anna Llach ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Membrane Potential ◽  
Dilated Cardiomyopathy ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Dna Intercalation ◽  
Antitumoral Activity ◽  
Ros Generation

Rationale: The widely used chemotherapeutic agent Doxorubicin (Dox) induces cardiotoxicity leading to dilated cardiomyopathy and heart failure. This cardiotoxicity has been related to ROS generation, DNA intercalation, bioenergetic distress and cell death. However, alternative mechanisms are emerging, focusing on signaling pathways. Objective: We investigated the role of Exchange Protein directly Activated by cAMP (EPAC), key factor in cAMP signaling, in Dox-induced cardiotoxicity. Methods and Results: Dox was administrated in vivo (10 +/- 2 mg/kg, i.v.; with analysis at 2, 6 and 15 weeks post injection) in WT and EPAC1 KO C57BL6 mice. Cardiac function was analyzed by echocardiography and intracellular Ca2+ homeostasis by confocal microscopy in isolated ventricular cardiomyocytes. 15 weeks post-injections, Dox-treated WT mice, developed a dilated cardiomyopathy with decreased ejection fraction, increased telediastolic volume and impaired Ca2+ homeostasis, which were totally prevented in the EPAC1 KO mice. The underlying mechanisms were investigated in neonatal and adult rat cardiac myocytes under Dox treatment (1-10 uM). Flow cytometry, Western blot, BRET sensor assay, and RT-qPCR analysis showed that Dox induced DNA damage and cardiomyocyte cell death with apoptotic features rather than necrosis, including Ca2+-CaMKKβ-dependent opening of the Mitochondrial Permeability Transition Pore, dissipation of the Mitochondrial membrane potential, caspase activation, cell size reduction, and DNA fragmentation. Dox also led to an increase in both cAMP concentration and EPAC1 protein level and activity. The pharmacological inhibition of EPAC1 (CE3F4) but not EPAC2 alleviated the whole Dox-induced pattern of alterations including DNA damage, Mitochondrial membrane potential, apoptosis, mitochondrial biogenesis, dynamic, and fission/fusion balance, and respiratory chain activity, suggesting a crucial role of EPAC1 in these processes. Importantly, while preserving cardiomyocyte integrity, EPAC1 inhibition potentiated Dox-induced cell death in several human cancer cell lines. Conclusion: Thus, EPAC1 inhibition could be a valuable therapeutic strategy to limit Dox-induced cardiomyopathy without interfering with its antitumoral activity.

scholarly journals Role of Prefrontal Cortex on Recognition Memory Deficits in Rats following 6-OHDA-Induced Locus Coeruleus Lesion

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Tuane Bazanella Sampaio ◽  
Naiani Ferreira Marques ◽  
Luisa Bandeira Binder ◽  
Carla Inês Tasca ◽  
Rui Daniel Prediger
Keyword(s):  
Prefrontal Cortex ◽  
Membrane Potential ◽  
Recognition Memory ◽  
Locus Coeruleus ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Membrane Damage ◽  
Memory Deficits ◽  
Parkinson’S Diseases

Degeneration of the locus coeruleus (LC), the main source of cerebral noradrenaline (NA), has been reported in diverse neurodegenerative diseases, including Parkinson’s diseases (PD). There is increasing evidence indicating the role of NA deficiency in the prefrontal cortex (PFC) and the development of early cognitive impairments in PD. Here, we evaluated whether a selective noradrenergic lesion of LC caused by 6-hydroxydopamine (6-OHDA) may induce memory deficits and neurochemical alterations in the PFC. Adult male Wistar rats received stereotaxic bilateral injections of 6-OHDA (5 μg/2 μl) into the LC, and two stainless-steel guide cannulas were implanted in the PFC. The SHAM group received just vehicle. To induce a selective noradrenergic lesion, animals received nomifensine (10 mg/kg), a dopamine transporter blocker, one hour before surgery. 6-OHDA-lesioned rats displayed impairments of the short- and long-term object recognition memory associated to reduced content of tyrosine hydroxylase in the LC. Neurochemical analysis revealed an altered mitochondrial membrane potential in LC. Regarding the PFC, an increased ROS production, cell membrane damage, and mitochondrial membrane potential disruption were observed. Remarkably, bilateral NA (1 μg/0.2 μl) infusion into the PFC restored the recognition memory deficits in LC-lesioned rats. These findings indicate that a selective noradrenergic LC lesion induced by 6-OHDA deregulates a noradrenergic network in the PFC, which could be involved in the early memory impairments observed in nondemented PD patients.

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