Blocking c-Jun N-terminal Kinase (JNK) Translocation to the Mitochondria Prevents 6-Hydroxydopamine-induced Toxicity in Vitro and in Vivo

Chambers, Jeremy W.; Howard, Shannon; LoGrasso, Philip V.

doi:10.1074/jbc.m112.421354

Cited by 63 publications

(70 citation statements)

References 24 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SH3BP5 also interacts with c‐Jun NH2‐terminal kinase (JNK) 19, which is required for survival and proliferation of B‐cell lymphoma cells 20, 21. The endogenous level of SH3BP5 positively regulates JNK 22, 23; however, the overexpressed SH3BP5 inhibits JNK 24. If SH3BP5 in DLBCL cells acts similarly as that in normal B cells, these findings suggest that SH3BP5 overexpression in DLBCL patients might be associated with a favorable prognosis.…”

Section: Discussionmentioning

confidence: 99%

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

et al. 2016

View full text Add to dashboard Cite

Diffuse large B‐cell lymphoma (DLBCL) is clinicopathologically and genetically heterogeneous with variable clinical outcomes. We previously identified signature genes overexpressed in CD5‐positive (CD5+) DLBCL, which is a poor prognostic subgroup of DLBCL. To elucidate the clinical significance of the protein expression of the signature genes overexpressed in CD5+ DLBCL with regard to all DLBCL, not otherwise specified (NOS), 10 genes (SH3BP5,LMO3,SNAP25,SYT5,SV2C,CABP1,FGF1,FGFR2,NEUROD1, and SYN2) were selected and examined immunohistochemically with samples from 28 patients with DLBCL, NOS. Only three protein expressions, SH3BP5, LMO3, and SNAP25, were detected in DLBCL cells and then analyzed further with samples from 187 patients with DLBCL, NOS. The SH3BP5, LMO3, and SNAP25 proteins were expressed in 60% (103/173), 34% (59/175), and 46% (77/168) of DLBCL patients, respectively. These protein expressions were associated with CD5 expression, and only SH3BP5 was frequently expressed in activated B‐cell‐like DLBCL (P = 0.046). Compared to the SH3BP5‐negative group, the SH3BP5+ group was correlated with elderly onset (>60 years, P = 0.0096) and advanced‐stage disease (stage III/IV, P = 0.037). The LMO3+ group showed a worse performance status (>1, P = 0.0004). The SH3BP5+ group and the LMO3+ group had significantly worse overall survival than the negative groups (P = 0.030, 0.034; respectively) for the entire group. In a subgroup analysis of patients treated with rituximab‐containing chemotherapy, there was no significant difference between groups. To the best of our knowledge, this is the first report showing the protein expressions of SH3BP5, LMO3, and SNAP25 in DLBCL cells and their clinical significance in patients with DLBCL. The SH3BP5 and LMO3 protein expressions are associated with the baseline clinical characteristics of DLBCL.

show abstract

Section: Discussionmentioning

confidence: 99%

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Elevated intracellular calcium concentration and mitochondrial membrane potential in SH-SY5Y cells may contribute to necrotic cell death. A previous study demonstrated that 6-OHDA treatment induced mitochondrial dysfunction in SH-SY5Y cells by activating the mitochondrial translocation of c-Jun N-terminal kinase (JNK) (17). Hence, other molecular signals, such as those of JNK, may be involved in 6-OHDA-mediated cytotoxicity in SH-SY5Y cells.…”

Section: Discussionmentioning

confidence: 99%

Stimulus-dependent neuronal cell responses in SH-SY5Y neuroblastoma cells

Sun

Shi

et al. 2016

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. The aim of the present study was to elucidate the intracellular mechanisms that cause neuronal cell death following exposure to excitatory neurotransmitter-induced neurotoxicity, neurotoxins and oxidative stress. Human SH-SY5Y neuroblastoma cells were exposed to various stimuli, including glutamate, 6-hydroxydopamine (6-OHDA), and glucose oxidase, and cell viability was determined by MTT assay. Early apoptosis and necrosis were examined by Annexin V/propidium iodide double staining and flow cytometric analysis. Intracellular calcium ion concentration and mitochondrial membrane potential were assessed by Fluo-3a and JC-1 staining, respectively. In addition, protein expression of receptor-interacting protein (RIP) kinase 1 and RIP kinase 3 were evaluated by western blotting. Glutamate, 6-OHDA and glucose oxidase treatment decreased cell viability. Glutamate induced apoptosis and necrosis, whereas, 6-OHDA induced cell necrosis and glucose oxidase induced apoptosis. Furthermore, glutamate, 6-OHDA or glucose oxidase treatment significantly increased intracellular calcium concentrations (P<0.05). The effect of glutamate on mitochondrial membrane potential varied with high and low concentrations, whereas 6-OHDA and glucose oxidase significantly increased the mitochondrial membrane potential in the SH-SY5Y cells (P<0.05). Glutamate significantly upregulated expression levels of RIP kinase 1 (P<0.05), but not RIP kinase 3. These findings demonstrate that the response of SH-SY5Y cells varies with the stimuli. Furthermore, RIP kinase 1 may specifically regulate programmed necrosis in glutamate-mediated excitatory toxicity, but not in cell damage induced by either 6-OHDA or glucose oxidase.

show abstract

“…Under conditions of stress, activated JNK translocates to the mitochondria, inhibits mitochondrial respiration, and can induce apoptosis via a permeability transition pore dependent or independent mechanism, resulting in the release of proapoptotic factors from the mitochondria such as Cytc [79, 80]. As expected, suppression of JNK translocation to the mitochondria protects mitochondrial integrity and function [81]. It was shown that JNK translocates to the mitochondrial outer membrane where it phosphorylates pyruvate dehydrogenase, leading to enzyme inhibition and thus limited substrate delivery for the Krebs cycle and OxPhos [82].…”

Section: Role Of Oxidative Phosphorylation In Acute Inflammationmentioning

confidence: 98%

Energy crisis: The role of oxidative phosphorylation in acute inflammation and sepsis

Lee

Hüttemann

2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

130

View full text Add to dashboard Cite

Mitochondrial dysfunction is increasingly recognized as an accomplice in most of the common human diseases including cancer, neurodegeneration, diabetes, ischemia/reperfusion injury as seen in myocardial infarction and stroke, and sepsis. Inflammatory conditions, both acute and chronic, have recently been shown to affect mitochondrial function. We here discuss the role of oxidative phosphorylation (OxPhos), focusing on acute inflammatory conditions, in particular sepsis and experimental sepsis models. We discuss mitochondrial alterations, specifically suppression of oxidative metabolism and the role of mitochondrial reactive oxygen species in disease pathology. Several signaling pathways including metabolic, proliferative, and cytokine signaling affect mitochondrial function and appear to be important in inflammatory disease conditions. Cytochrome c oxidase (COX) and cytochrome c, the latter of which plays a central role in apoptosis in addition to mitochondrial respiration, serve as examples for the entire OxPhos system since they have been studied in more detail with respect to cell signaling. We propose a model in which inflammatory signaling leads to changes in the phosphorylation state of mitochondrial proteins, including Tyr304 phosphorylation of COX catalytic subunit I. This results in inhibition of OxPhos, a reduction of the mitochondrial membrane potential, and consequently a lack of energy, which can cause organ failure and death as seen in septic patients.

show abstract

Blocking c-Jun N-terminal Kinase (JNK) Translocation to the Mitochondria Prevents 6-Hydroxydopamine-induced Toxicity in Vitro and in Vivo

Cited by 63 publications

References 24 publications

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

Stimulus-dependent neuronal cell responses in SH-SY5Y neuroblastoma cells

Energy crisis: The role of oxidative phosphorylation in acute inflammation and sepsis

Contact Info

Product

Resources

About