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Flow Cytometric Analysis of Apoptotic Biomarkers in Actinomycin D-Treated SiHa Cervical Cancer Cells
Published on: August 26, 2021
VDAC blockage by phosphorothioate oligonucleotides and its implication in apoptosis
1Farber Institute for Neurosciences, Weinberg Unit for ALS Research, Thomas Jefferson University, Philadelphia, PA 19107, USA. wenzhi.tan@jefferson.edu
Biochimica Et Biophysica Acta
|January 13, 2012
Summary
Voltage-dependent anion channel (VDAC) gating influences cytochrome c release and apoptosis. Blockage of VDAC by G3139, a phosphorothioate oligonucleotide, demonstrates VDAC
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Apoptosis is vital for multicellular organism homeostasis, with dysregulation implicated in cancer and neurodegenerative diseases.
- The intrinsic apoptotic pathway involves cytochrome c release from mitochondria.
- Voltage-dependent anion channel (VDAC) regulates metabolite flux across the mitochondrial outer membrane (MOM).
Purpose of the Study:
- To review evidence linking VDAC gating and MOM permeability to cytochrome c release and apoptosis.
- To highlight the role of VDAC in initiating apoptosis, particularly through its blockage.
Main Methods:
- Review of recent research on VDAC conducting states and their influence on cytochrome c release.
- Analysis of evidence for VDAC blockage by G3139, a phosphorothioate oligonucleotide, and its proapoptotic activity.
- Examination of shared characteristics between VDAC blockage and proapoptotic activity of G3139.
Main Results:
- VDAC gating and subsequent changes in MOM permeability influence cytochrome c release and apoptosis.
- Blockage of VDAC by G3139 provides strong evidence for VDAC's role in initiating apoptosis.
- Proapoptotic activity of G3139 and VDAC blockage share dependencies on phosphorothioate modification, oligonucleotide length, and sequence independence.
Conclusions:
- MOM permeability regulated by VDAC gating is crucial for mitochondrial function and apoptosis control.
- VDAC plays a significant role in the initiation and regulation of apoptosis.
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