TNFalpha induces apoptosis through JNK/Bax-dependent pathway in differentiated, but not naïve PC12 cells. 2007

Lan Zhang, and Da Xing, and Lei Liu, and Xuejuan Gao, and Miaojuan Chen
MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, South China Normal University, Guangzhou, China.

Differentiated PC12 cells have been used widely as a model for the analysis of neuronal degeneration. Some evidences showed that differentiated PC12 cells were more sensitive than naïve PC12 against apoptosis stimuli. However, the apoptosis mechanism of both types of PC12 cells was not fully known. In this study, the signaling pathways involved in tumor necrosis factor-alpha (TNFalpha)-induced apoptosis in living differentiated and naïve PC12 cells were investigated using confocal microscope for the first time. Our results showed that during TNFalpha-induced apoptosis, Bax translocation to mitochondria and cytochrome C (Cyt c) release from mitochondria were observed in differentiated PC12 cells, but not in naïve PC12 cells. Furthermore, the mRNA levels of bim, c-Jun N-terminal protein kinase 1 and 2 (JNK1 and JNK2) increased noticeably in differentiated PC12 cells. The apoptosis induced by TNFalpha was inhibited by Z-IETD-fmk (specific inhibitor of caspase-8) but not SP600125 (specific inhibitor of JNK) in naïve PC12 cells. While in differentiated PC12 cells, the process of apoptosis could only be inhibited effectively by Z-IETD-fmk and SP600125 cotreatment, and SP600125 inhibited the Bax translocation to mitochondria implying that JNK mediated activation of Bax. The experimental data strongly demonstrated that TNFalpha induced apoptosis through JNK/Bax-dependent pathway in differentiated, but not naïve PC12 cells.

UI MeSH Term Description Entries
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D009842 Oligopeptides Peptides composed of between two and twelve amino acids. Oligopeptide
D011518 Proto-Oncogene Proteins Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. Cellular Proto-Oncogene Proteins,c-onc Proteins,Proto Oncogene Proteins, Cellular,Proto-Oncogene Products, Cellular,Cellular Proto Oncogene Proteins,Cellular Proto-Oncogene Products,Proto Oncogene Products, Cellular,Proto Oncogene Proteins,Proto-Oncogene Proteins, Cellular,c onc Proteins
D000072224 Bcl-2-Like Protein 11 A BCL-2-like protein that has a C-terminal BCL-2 homology (BH3) domain and forms heterodimers with other BCL-2 FAMILY PROTEINS. It is a strong inducer of APOPTOSIS and ANOIKIS; several isoforms are expressed (BimEL, Bim L, Bim-alpha, Bim-s; and Bim-gamma) that have different potencies for inducing apoptosis. BCL2L11 Protein,BIM Protein,Bcl-2-Binding Protein, BIM,Bcl-2-Interacting Mediator of Cell Death,11, Bcl-2-Like Protein,BIM Bcl-2-Binding Protein,Bcl 2 Binding Protein, BIM,Bcl 2 Interacting Mediator of Cell Death,Bcl 2 Like Protein 11,Protein 11, Bcl-2-Like,Protein, BCL2L11,Protein, BIM,Protein, BIM Bcl-2-Binding
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000873 Anthracenes A group of compounds with three aromatic rings joined in linear arrangement.
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal

Related Publications

Lan Zhang, and Da Xing, and Lei Liu, and Xuejuan Gao, and Miaojuan Chen
March 2016, Genetics and molecular research : GMR,
Lan Zhang, and Da Xing, and Lei Liu, and Xuejuan Gao, and Miaojuan Chen
March 2013, Phytotherapy research : PTR,
Lan Zhang, and Da Xing, and Lei Liu, and Xuejuan Gao, and Miaojuan Chen
October 2003, Cell,
Lan Zhang, and Da Xing, and Lei Liu, and Xuejuan Gao, and Miaojuan Chen
April 2017, Neurochemical research,
Lan Zhang, and Da Xing, and Lei Liu, and Xuejuan Gao, and Miaojuan Chen
September 2016, European journal of pharmacology,
Lan Zhang, and Da Xing, and Lei Liu, and Xuejuan Gao, and Miaojuan Chen
June 2011, Neuroscience letters,
Lan Zhang, and Da Xing, and Lei Liu, and Xuejuan Gao, and Miaojuan Chen
January 2005, Oncology reports,
Lan Zhang, and Da Xing, and Lei Liu, and Xuejuan Gao, and Miaojuan Chen
August 2013, European review for medical and pharmacological sciences,
Lan Zhang, and Da Xing, and Lei Liu, and Xuejuan Gao, and Miaojuan Chen
November 2011, Oncology letters,
Lan Zhang, and Da Xing, and Lei Liu, and Xuejuan Gao, and Miaojuan Chen
May 2004, Journal of pharmacological sciences,
Copied contents to your clipboard!