Free cholesterol overloading induced smooth muscle cells death and activated both ER- and mitochondrial-dependent death pathway

Autor: Yan Ming, Yang Yi, Xu Kedi, Wang Yongping, Zheng Xiao-xiang
Rok vydání: 2009
Předmět:
medicine.medical_specialty
Programmed cell death
Necrosis
Time Factors
Myocytes
Smooth Muscle
Apoptosis
Biology
Mitochondrion
Endoplasmic Reticulum
Muscle
Smooth
Vascular
chemistry.chemical_compound
Downregulation and upregulation
Internal medicine
medicine
Myocyte
Animals
HSP70 Heat-Shock Proteins
Organosilicon Compounds
Propidium iodide
Enzyme Inhibitors
Cells
Cultured
Heat-Shock Proteins
bcl-2-Associated X Protein
Membrane Potential
Mitochondrial
Staining and Labeling
Endoplasmic reticulum
beta-Cyclodextrins
Cytochromes c
Membrane Proteins
Flow Cytometry
Amides
Cell biology
Mitochondria
Muscle
Rats
Oxidative Stress
Endocrinology
Cholesterol
chemistry
Unfolded protein response
Unfolded Protein Response
medicine.symptom
Cardiology and Cardiovascular Medicine
Reactive Oxygen Species
Transcription Factor CHOP
Foam Cells
Signal Transduction
Sterol O-Acyltransferase
Zdroj: Atherosclerosis. 207(1)
ISSN: 1879-1484
Popis: Smooth muscle cells (SMCs) death promotes atherosclerotic lesion necrosis and plaque destabilization. We investigated the potential mechanisms of rat SMCs death in response to excess free cholesterol (FC).Rat aortic SMCs were incubated with "water soluble cholesterol" and acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor Sandoz58035 to establish FC-overloading cell model. Disruption of mitochondrial network and endoplasmic reticulum (ER) was observed after 12h incubation by transient transfection. After treated for 24h, enhanced cell death was noted as detected by propidium iodide (PI) staining/flow cytometry (P0.001 vs. control). SMCs death was associated with markedly decreased mitochondrial transmembrane potential (Deltaphim), as well as upregulation of cellular reactive oxygen species (ROS) and ER stress. We also investigated possible signaling pathways involved in excess FC-initiated cell death and found that unfolded protein response (UPR) was activated, with increased cellular Bax expression and release of mitochondrial cytochrome c.Our findings suggested that FC-overloading might trigger SMCs death. Both ER- and mitochondria-based signals might be implicated in these lethal events.
Databáze: OpenAIRE
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