Cell-Derived Vesicles as TRPC1 Channel Delivery Systems for the Recovery of Cellular Respiratory and Proliferative Capacities
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Date
2020-11
Publication Type
Journal Article
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yes
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Abstract
Pulsed electromagnetic fields (PEMFs) are capable of specifically activating a TRPC1‐mitochondrial axis underlying cell expansion and mitohormetic survival adaptations. This study characterizes cell‐derived vesicles (CDVs) generated from C2C12 murine myoblasts and shows that they are equipped with the sufficient molecular machinery to confer mitochondrial respiratory capacity and associated proliferative responses upon their fusion with recipient cells. CDVs derived from wild type C2C12 myoblasts include the cation‐permeable transient receptor potential (TRP) channels, TRPC1 and TRPA1, and directly respond to PEMF exposure with TRPC1‐mediated calcium entry. By contrast, CDVs derived from C2C12 muscle cells in which TRPC1 has been genetically knocked‐down using CRISPR/Cas9 genome editing, do not. Wild type C2C12‐derived CDVs are also capable of restoring PEMF‐induced proliferative and mitochondrial activation in two C2C12‐derived TRPC1 knockdown clonal cell lines in accordance to their endogenous degree of TRPC1 suppression. C2C12 wild type CDVs respond to menthol with calcium entry and accumulation, likewise verifying TRPA1 functional gating and further corroborating compartmental integrity. Proteomic and lipidomic analyses confirm the surface membrane origin of the CDVs providing an initial indication of the minimal cellular machinery required to recover mitochondrial function. CDVs hence possess the potential of restoring respiratory and proliferative capacities to senescent cells and tissues.
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published
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Journal / series
Volume
4 (11)
Pages / Article No.
2000146
Publisher
Wiley-VCH
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Date collected
Date created
Subject
cell‐derived vesicles; CRISPR/Cas9 genome editing; mitochondrial respiration; pulsed magnetic fields; TRPC1 cation channel
Organisational unit
08839 - Zamboni, Nicola (Tit.-Prof.)
03807 - Dittrich, Petra / Dittrich, Petra
Notes
Funding
160259 - Direct identification of lateral protein interactions in the plasma membrane of living cells and tissues (SNF)