title: The Relationship between the Bcl-2/Bax Proteins and the Mitochondria-Mediated Apoptosis Pathway in the Differentiation of Adipose-Derived Stromal Cells into Neurons.
abstract: Our objective is to study the relationship between the regulatory proteins Bcl-2/Bax and mitochondria-mediated apoptosis during the differentiation of adipose-derived stromal cells (ADSCs) into neurons. Immunocytochemistry and western blotting showed that the cells weakly expressed neuron-specific enolase (NSE) in the non-induced group and expressed NSE more strongly in the groups induced for 1 h, 3 h, 5 h and 8 h. NSE expression peaked at 5 h (P < 0.05), although there was no significant difference between 5 and 8 h (P > 0.05). Bcl-2 expression gradually decreased over time in the non-induced group (P < 0.05). However, Bax, caspase-9, Cyt-c and caspase-3 expression gradually increased and peaked at 8 h (P < 0.05). Transmission electron microscopy revealed karyopyknosis, chromatin edge setting, mitochondria swelling and cavitation in cells at 5 h, and the mitochondrial membrane potential decreased over time, as demonstrated by laser scanning confocal microscopy. After a 5 h induction, cells differentiated into typical neurons and expressed Bcl-2, which inhibited apoptosis. Bax showed a strong apoptosis-promoting capacity, leading to changes in the mitochondrial membrane potential and structure, and then triggered the caspase-independent apoptotic response through the mitochondrial pathway. At the same time, Cyt-c was directly or indirectly released from the mitochondria to the cytoplasm to trigger the caspase-dependent apoptotic response through the mitochondrial pathway. Therefore, Bcl-2/Bax play an important role in regulating caspase-dependent and caspase-independent apoptosis mediated by the mitochondrial pathway during the differentiation of ADSCs into neurons.
authors.affiliation: Department of Neurology, Affiliated Kailuan General Hospital of North China, University of Science and Technology, Tangshan, 063000, Hebei Province, China.
authors.forename: Quanquan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Neurology, Affiliated Kailuan General Hospital of North China, University of Science and Technology, Tangshan, 063000, Hebei Province, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Affiliated Kailuan General Hospital of North China, University of Science and Technology, Tangshan, 063000, Hebei Province, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Neurology, Affiliated Kailuan General Hospital of North China, University of Science and Technology, Tangshan, 063000, Hebei Province, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Ou
authors.affiliation: Department of Neurology, Affiliated Kailuan General Hospital of North China, University of Science and Technology, Tangshan, 063000, Hebei Province, China.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Affiliated Kailuan General Hospital of North China, University of Science and Technology, Tangshan, 063000, Hebei Province, China.
authors.forename: Zanzan
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Neurological and Biological Function of Hebei Province, Tangshan, 063000, Hebei Province, China.
authors.forename: Pingshu
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Neurology of Tangshan, Tangshan, 063000, Hebei Province, Tangshan, 063000, Hebei Province, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Neurology, Affiliated Kailuan General Hospital of North China, University of Science and Technology, Tangshan, 063000, Hebei Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Neurology, Affiliated Kailuan General Hospital of North China, University of Science and Technology, Tangshan, 063000, Hebei Province, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053078:Membrane Potential, Mitochondrial; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9