Oxidative stress, proteasome impairment and mitochondrial dysfunction are implicated as contributors to ageing and neurodegeneration. Using mouse neuronal cells, we showed previously that the reversible proteasome inhibitor, [N-benzyloxycarbonyl-Ile-Glu (O-t-bytul)-Ala-leucinal; (PSI)] induced excessive reactive oxygen species (ROS) that mediated mitochondrial damage and a caspase-independent cell death. Herein, we examined whether this insult persists in neuronal cells recovering from inhibitor removal over time. Recovery from proteasome inhibition showed a time and dose-dependent cell death that was accompanied by ROS overproduction, caspase activation and mitochondrial membrane permeabilization with the subcellular relocalizations of the proapoptotic proteins, Bax, cytochrome c and the apoptosis inducing factor (AIF). Caspase inhibition failed to promote survival indicating that cell death was caspase-independent. Treatments with the antioxidant N-acetyl-cysteine (NAC) were needed to promote survival in cell recovering from mild proteasome inhibition while overexpression of the antiapoptotic protein Bcl-xL together with NAC attenuated cell death during recovery from potent inhibition. Whereas inhibitor removal increased prot...Continue Reading
BH4 domain of antiapoptotic Bcl-2 family members closes voltage-dependent anion channel and inhibits apoptotic mitochondrial changes and cell death
Separation of cathepsin A-like enzyme and the proteasome: evidence that lactacystin/beta-lactone is not a specific inhibitor of the proteasome
Bcl-xL promotes the open configuration of the voltage-dependent anion channel and metabolite passage through the outer mitochondrial membrane
VDAC-dependent permeabilization of the outer mitochondrial membrane by superoxide induces rapid and massive cytochrome c release
Proteasome inhibitors induce intracellular protein aggregation and cell death by an oxygen-dependent mechanism
Mitochondrial dysfunction due to mutant copper/zinc superoxide dismutase associated with amyotrophic lateral sclerosis is reversed by N-acetylcysteine
Mitochondrial release of AIF and EndoG requires caspase activation downstream of Bax/Bak-mediated permeabilization
Reactive oxygen species are required for hyperoxia-induced Bax activation and cell death in alveolar epithelial cells.
The hierarchical relationship between MAPK signaling and ROS generation in human leukemia cells undergoing apoptosis in response to the proteasome inhibitor Bortezomib
Decreased proteolysis caused by protein aggregates, inclusion bodies, plaques, lipofuscin, ceroid, and 'aggresomes' during oxidative stress, aging, and disease
Application of proteasomal inhibitors to mouse sympathetic neurons activates the intrinsic apoptotic pathway
Inhibition of MG132-induced mitochondrial dysfunction and cell death in PC12 cells by 3-morpholinosydnonimine
Proteasome inhibition by MG-132 induces apoptotic cell death and mitochondrial dysfunction in cultured rat brain oligodendrocytes but not in astrocytes
Proteasomal dysfunction: a common feature of neurodegenerative diseases? Implications for the environmental origins of neurodegeneration
Simultaneous age-related depolarization of mitochondrial membrane potential and increased mitochondrial reactive oxygen species production correlate with age-related glutamate excitotoxicity in rat hippocampal neurons
NPI-0052, a novel proteasome inhibitor, induces caspase-8 and ROS-dependent apoptosis alone and in combination with HDAC inhibitors in leukemia cells
Reactive oxygen species induced by proteasome inhibition in neuronal cells mediate mitochondrial dysfunction and a caspase-independent cell death
Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders
Delayed treatment with vitamin C and N-acetyl-L-cysteine protects Schwann cells without compromising the anti-myeloma activity of bortezomib
Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast
A mechanistic study of proteasome inhibition-induced iron misregulation in dopamine neuron degeneration
Proteasome inhibition represses unfolded protein response and Nox4, sensitizing vascular cells to endoplasmic reticulum stress-induced death
Current understanding on the role of standard and immunoproteasomes in inflammatory/immunological pathways of multiple sclerosis
Redox-regulated pathway of tyrosine phosphorylation underlies NF-κB induction by an atypical pathway independent of the 26S proteasome
Insulin-like growth factor-I mediates neuroprotection in proteasome inhibition-induced cytotoxicity in SH-SY5Y cells
Oxidative modification of mitochondrial integrity and nerve fiber density in the ischemic overactive bladder
A Bowman-Birk inhibitor induces apoptosis in human breast adenocarcinoma through mitochondrial impairment and oxidative damage following proteasome 20S inhibition
Synergistic stress exacerbation in hippocampal neurons: Evidence favoring the dual-hit hypothesis of neurodegeneration
Synergistic neuroprotective effect of schisandrin and nootkatone on regulating inflammation, apoptosis and autophagy via the PI3K/AKT pathway
Berberine attenuated the cytotoxicity induced by t-BHP via inhibiting oxidative stress and mitochondria dysfunction in PC-12 cells
Negative regulation of 26S proteasome stability via calpain-mediated cleavage of Rpn10 subunit upon mitochondrial dysfunction in neurons.
Effect of Initial Aging and High-Fat/High-Fructose Diet on Mitochondrial Bioenergetics and Oxidative Status in Rat Brain
BCL-2 Family Proteins
BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.
Cell Aging (Keystone)
This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.
This feed focuses on cellular aging with emphasis on mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.