Voltage-dependent anion channel (VDAC) participates in amyloid beta-induced toxicity and interacts with plasma membrane estrogen receptor alpha in septal and hippocampal neurons.
Voltage-dependent anion channel (VDAC) is a porin known by its role in metabolite transport across mitochondria and participation in apoptotic processes. Although traditionally accepted to be located within mitochondrial outer membrane, some data has also reported its presence at the plasma membrane level where it seems to participate in regulation of normal redox homeostasis and apoptosis. Here, exposure of septal SN56 and hippocampal HT22 cells to specific anti-VDAC antibodies prior to amyloid beta (Abeta) peptide was observed to prevent neurotoxicity. In these cell lines, we identified a VDAC form associated with the plasma membrane that seems to be particularly abundant in caveolae. The two membrane-related isoforms of estrogen receptor alpha (mERalpha) (80 and 67 kDa), known in SN56 cells to participate in estrogen-induced neuroprotection against Abeta injury, were also observed to be present in caveolae. Interestingly, we demonstrated for the first time that both VDAC and mERalpha interact at the plasma membrane of these neurons as well as in microsomal fractions of the corresponding murine septal and hippocampal tissues. These proteins were also shown to associate with caveolin-1, thereby corroborating their presence in caveolar microdomains. Taken together, these results suggest that VDAC-mERalpha association at the plasma membrane level may participate in the modulation of Abeta-induced cell death.
Marin
Raquel
R
Laboratory of Cellular Neurobiology, Department of Physiology & Institute of Biomedical Technologies, University of La Laguna, School of Medicine, Santa Cruz de Tenerife, Spain. rmarin@ull.es
Ramírez
Cristina M
CM
González
Miriam
M
González-Muñoz
Elena
E
Zorzano
Antonio
A
Camps
Marta
M
Alonso
Rafael
R
Díaz
Mario
M
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D020665:Septum of Brain / Q000378:metabolism*; D050994:Voltage-Dependent Anion Channels / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*
D016229:Amyloid beta-Peptides; D000906:Antibodies; D047628:Estrogen Receptor alpha; D050994:Voltage-Dependent Anion Channels