BIOMAT Database Logo BIOMAT Database Logo

Involvement of CaM-CaMKII-ERK in bisphenol A-induced Sertoli cell apoptosis. 2014

Wenyi Qian, and Jingying Zhu, and Changfei Mao, and Jingli Liu, and Yixin Wang, and Qiang Wang, and Yanqing Liu, and Rong Gao, and Hang Xiao, and Jun Wang
Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.

Bisphenol A (BPA), one of the most prevalent chemicals for daily use, has been reported as a xenoestrogen to induce reproductive toxicity, but its mechanism is poorly understood. In the present study, we aimed to explore whether CaM-CaMKII-ERK1/2 signaling pathway was involved in BPA-induced Sertoli cells injury via the mitochondrial apoptotic pathway. TM4 cells were cultured with 0, 0.02, 0.2, 2.0, 20μM BPA, and cell viability, mitochondrial function and CaM-CaMKII-ERK1/2 signal pathway were examined. With the MTT assay, BPA was found to suppress cell viability in a dose- and time-dependent manner. Moreover, mitochondrial mass loss, membrane potential decrease, cytochrome c release, Bcl-2 family members down-regulation and caspases-3 up-regulation were obviously observed when the TM4 cells were exposed to BPA. Additionally, the expression of calmodulin (CaM) and phosphorylation of calcium/calmodulin dependent kinase II (CaMKII) significantly increased, and pretreatment with 10μM antagonist of CaM (W-7) or CaMKII (KN62) prevented cell damage through mitochondrial apoptotic pathway. In parallel, ERK1/2 pathway was proved to participate in BPA-induced cell damage, since W-7 and KN62 partially suppressed ERK1/2 activation, and PD98059, the ERK1/2 antagonist, significantly attenuated BPA-induced cell damage. These data, taken together, indicated that CaM-CaMKII-ERK axis might transmit apoptotic signals to the mitochondria during BPA-induced cell apoptosis. By exploring the mechanisms of the Ca(2+) homeostasis and the corresponding proteins, our study provides new insight into BPA-induced reproductive toxicity.

UI MeSH Term Description Entries
D008297 Male Males
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
D010636 Phenols Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D002147 Calmodulin A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. Calcium-Dependent Activator Protein,Calcium-Dependent Regulator,Bovine Activator Protein,Cyclic AMP-Phosphodiesterase Activator,Phosphodiesterase Activating Factor,Phosphodiesterase Activator Protein,Phosphodiesterase Protein Activator,Regulator, Calcium-Dependent,AMP-Phosphodiesterase Activator, Cyclic,Activating Factor, Phosphodiesterase,Activator Protein, Bovine,Activator Protein, Calcium-Dependent,Activator Protein, Phosphodiesterase,Activator, Cyclic AMP-Phosphodiesterase,Activator, Phosphodiesterase Protein,Calcium Dependent Activator Protein,Calcium Dependent Regulator,Cyclic AMP Phosphodiesterase Activator,Factor, Phosphodiesterase Activating,Protein Activator, Phosphodiesterase,Protein, Bovine Activator,Protein, Calcium-Dependent Activator,Protein, Phosphodiesterase Activator,Regulator, Calcium Dependent
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
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

Related Publications

Wenyi Qian, and Jingying Zhu, and Changfei Mao, and Jingli Liu, and Yixin Wang, and Qiang Wang, and Yanqing Liu, and Rong Gao, and Hang Xiao, and Jun Wang
Bisphenol A-induced apoptosis of cultured rat Sertoli cells.
January 2003, Reproductive toxicology (Elmsford, N.Y.),
Wenyi Qian, and Jingying Zhu, and Changfei Mao, and Jingli Liu, and Yixin Wang, and Qiang Wang, and Yanqing Liu, and Rong Gao, and Hang Xiao, and Jun Wang
NMDARs antagonist MK801 suppresses LPS-induced apoptosis and mitochondrial dysfunction by regulating subunits of NMDARs via the CaM/CaMKII/ERK pathway.
February 2023, Cell death discovery,
Wenyi Qian, and Jingying Zhu, and Changfei Mao, and Jingli Liu, and Yixin Wang, and Qiang Wang, and Yanqing Liu, and Rong Gao, and Hang Xiao, and Jun Wang
Molecular changes induced by bisphenol-A in rat Sertoli cell culture.
October 2011, Systems biology in reproductive medicine,
Wenyi Qian, and Jingying Zhu, and Changfei Mao, and Jingli Liu, and Yixin Wang, and Qiang Wang, and Yanqing Liu, and Rong Gao, and Hang Xiao, and Jun Wang
Bisphenol A affects cell viability involved in autophagy and apoptosis in goat testis sertoli cell.
October 2017, Environmental toxicology and pharmacology,
Wenyi Qian, and Jingying Zhu, and Changfei Mao, and Jingli Liu, and Yixin Wang, and Qiang Wang, and Yanqing Liu, and Rong Gao, and Hang Xiao, and Jun Wang
The involvement of CaM-KII in insulin induced cell proliferation.
July 2009, Cell cycle (Georgetown, Tex.),
Wenyi Qian, and Jingying Zhu, and Changfei Mao, and Jingli Liu, and Yixin Wang, and Qiang Wang, and Yanqing Liu, and Rong Gao, and Hang Xiao, and Jun Wang
Involvement of AMPKα and MAPK-ERK/-JNK Signals in Docetaxel-Induced Human Tongue Squamous Cell Carcinoma Cell Apoptosis.
November 2022, International journal of molecular sciences,
Wenyi Qian, and Jingying Zhu, and Changfei Mao, and Jingli Liu, and Yixin Wang, and Qiang Wang, and Yanqing Liu, and Rong Gao, and Hang Xiao, and Jun Wang
Nicotine-induced phosphorylation of ERK in mouse primary cortical neurons: evidence for involvement of glutamatergic signaling and CaMKII.
October 2007, Journal of neurochemistry,
Wenyi Qian, and Jingying Zhu, and Changfei Mao, and Jingli Liu, and Yixin Wang, and Qiang Wang, and Yanqing Liu, and Rong Gao, and Hang Xiao, and Jun Wang
Implications of Sertoli cell induced germ cell apoptosis to testicular pathology.
January 2014, Spermatogenesis,
Wenyi Qian, and Jingying Zhu, and Changfei Mao, and Jingli Liu, and Yixin Wang, and Qiang Wang, and Yanqing Liu, and Rong Gao, and Hang Xiao, and Jun Wang
Defective autophagic flux aggravates cadmium-induced Sertoli cell apoptosis.
March 2024, Ecotoxicology and environmental safety,
Wenyi Qian, and Jingying Zhu, and Changfei Mao, and Jingli Liu, and Yixin Wang, and Qiang Wang, and Yanqing Liu, and Rong Gao, and Hang Xiao, and Jun Wang
ERK and cell death: mechanisms of ERK-induced cell death--apoptosis, autophagy and senescence.
January 2010, The FEBS journal,
Copied contents to your clipboard!