Cyclosporin A enhances colchicine-induced apoptosis in rat cerebellar granule neurons. 2004

Anna Maria Canudas, and Elvira G Jordà, and Ester Verdaguer, and Andrés Jiménez, and Francesc Xavier Sureda, and Víctor Rimbau, and Antoni Camins, and Mercè Pallàs
Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona E-08028, Spain.

1. Cyclosporin A (CsA, 1-50 microM), an immunosuppressive drug with known neurotoxic effects, did not decrease the viability of primary cultures of rat cerebellar granule neurons (CGN) or induce apoptotic features. However, CsA specifically enhanced the cytotoxicity and apoptosis induced by colchicine (1 microM). 2. Flavopiridol, an inhibitor of cyclin-dependent kinases (CDKs), prevented the neurotoxic effects of colchicine plus CsA. At 0.1-5 microM, it also showed antiapoptotic effects, as revealed by propidium iodide staining, flow cytometry and counting of cell nuclei. 3. Roscovitine (25-50 microM), a selective cdk1, 2 and 5 inhibitor, showed an antiapoptotic effect against colchicine- and colchicine plus CsA-induced apoptosis. 4. CsA increased the expression of cdk5 and cdk5/p25 mediated by colchicine, a CDK involved in neuronal apoptosis. After treatment of CGN with colchicine plus CsA, the changes in the p25/p35 ratio pointed to cdk5 activation. 5. Immunohistochemical results showed a nuclear localization of cdk5 after neurotoxic treatment, which was prevented by cdk inhibitors. Thus, we propose a new mechanism of modulation of CsA neurotoxicity mediated by cdk5.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011726 Pyridinium Compounds Derivatives of PYRIDINE containing a cation C5H5NH or radical C5H6N. Compounds, Pyridinium
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
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002531 Cerebellum The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills. Cerebella,Corpus Cerebelli,Parencephalon,Cerebellums,Parencephalons
D003078 Colchicine A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (PERIODIC DISEASE). Colchicine, (+-)-Isomer,Colchicine, (R)-Isomer
D003594 Cytoplasmic Granules Condensed areas of cellular material that may be bounded by a membrane. Cytoplasmic Granule,Granule, Cytoplasmic,Granules, Cytoplasmic
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug

Related Publications

Anna Maria Canudas, and Elvira G Jordà, and Ester Verdaguer, and Andrés Jiménez, and Francesc Xavier Sureda, and Víctor Rimbau, and Antoni Camins, and Mercè Pallàs
September 1999, Neurochemical research,
Anna Maria Canudas, and Elvira G Jordà, and Ester Verdaguer, and Andrés Jiménez, and Francesc Xavier Sureda, and Víctor Rimbau, and Antoni Camins, and Mercè Pallàs
February 1999, Zhonghua yi xue za zhi,
Anna Maria Canudas, and Elvira G Jordà, and Ester Verdaguer, and Andrés Jiménez, and Francesc Xavier Sureda, and Víctor Rimbau, and Antoni Camins, and Mercè Pallàs
May 1995, Experimental cell research,
Anna Maria Canudas, and Elvira G Jordà, and Ester Verdaguer, and Andrés Jiménez, and Francesc Xavier Sureda, and Víctor Rimbau, and Antoni Camins, and Mercè Pallàs
January 1999, Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica,
Anna Maria Canudas, and Elvira G Jordà, and Ester Verdaguer, and Andrés Jiménez, and Francesc Xavier Sureda, and Víctor Rimbau, and Antoni Camins, and Mercè Pallàs
May 2002, The European journal of neuroscience,
Anna Maria Canudas, and Elvira G Jordà, and Ester Verdaguer, and Andrés Jiménez, and Francesc Xavier Sureda, and Víctor Rimbau, and Antoni Camins, and Mercè Pallàs
January 2015, Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition,
Anna Maria Canudas, and Elvira G Jordà, and Ester Verdaguer, and Andrés Jiménez, and Francesc Xavier Sureda, and Víctor Rimbau, and Antoni Camins, and Mercè Pallàs
January 1996, Neuroscience letters,
Anna Maria Canudas, and Elvira G Jordà, and Ester Verdaguer, and Andrés Jiménez, and Francesc Xavier Sureda, and Víctor Rimbau, and Antoni Camins, and Mercè Pallàs
July 2004, Neuroscience letters,
Anna Maria Canudas, and Elvira G Jordà, and Ester Verdaguer, and Andrés Jiménez, and Francesc Xavier Sureda, and Víctor Rimbau, and Antoni Camins, and Mercè Pallàs
April 2001, Neuroscience letters,
Anna Maria Canudas, and Elvira G Jordà, and Ester Verdaguer, and Andrés Jiménez, and Francesc Xavier Sureda, and Víctor Rimbau, and Antoni Camins, and Mercè Pallàs
September 2006, Neuropharmacology,
Copied contents to your clipboard!