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.

Cardiac glycoside sensitized hepatocellular carcinoma cells to TRAIL via ROS generation, p38MAPK, mitochondrial transition, and autophagy mediation

“…The generation of ROS, however, may result in an imbalance in the intracellular redox status, which then allows ROS to mediate MMP transition, mitochondrial release of cytochrome c into the cytosol, and caspase activation. The proapoptotic Bax protein induces mitochondrial dysfunction and cytochrome c release from the mitochondrion that interacts with a specific adapter, which in turn activates pro‐caspases to active caspases . We evaluated CGs capable of inducing the mitochondrial release of cytochrome c and alteration of Bax from the cytosol into mitochondria, and thus, evaluated MMP loss in the process.…”

“…The proapoptotic Bax protein induces mitochondrial dysfunction and cytochrome c release from the mitochondrion that interacts with a specific adapter, which in turn activates pro-caspases to active caspases. 46 We evaluated CGs capable of inducing the mitochondrial release of cytochrome c and alteration of Bax from the cytosol into mitochondria, and thus, evaluated MMP loss in the process. Moreover, NAC prevents Bcl-2 downregulations and protects against MMP loss, thus protecting cells from ROS and apoptotic cell death ( Figure 5).…”

Astragaloside IV reverses simvastatin‐induced skeletal muscle injury by activating the AMPK‐PGC‐1α signalling pathway

“…It also suggested that AS‐IV increased mitochondrial energy production. Bcl‐2 and Bax play a very important role in apoptosis (Korsmeyer, Shutter, Veis, Merry, & Oltvai, ) and also are critical in regulating the effects of mitochondrial membrane permeability (Wang et al, ) and mitochondrial respiratory chain function (Luo et al, ). A study showed that AS‐IV upregulated Bcl‐2 expression in cardiomyocytes (Luo et al, ).…”

Cinobufagin Promotes Cell Cycle Arrest and Apoptosis to Block Human Esophageal Squamous Cell Carcinoma Cells Growth <i>via</i> the p73 Signalling Pathway

“…In recent years, the phenomenon of cell cycle-mediated apoptosis has also received increasing attention and is an appre- ciated approach to eliminate cancer cells. 38,39) In this regard, cinobufagin is a promising chemical because it is capable of selectively or preferentially killing cancer cells by inhibiting cell cycle progression and/or inducing apoptosis. [21][22][23][24][25][26][27] This study initially revealed that cinobufagin treatment induced apoptosis of EC-109, Kyse-150 and Kyse-520 cells (Fig.…”