PMID: 11606804Oct 19, 2001Paper

Mechanisms of the apoptotic and necrotic actions of trimethyltin in cerebellar granule cells

Toxicological Sciences : an Official Journal of the Society of Toxicology
P G GunasekarG E Isom

Abstract

In evaluating mechanisms of trimethyltin (TMT)-initiated neuronal damage, the present study focused on involvement of reactive oxygen species, protein kinase C (PKC), and glutamate receptors. Exposure of cerebellar granule cells to TMT (0.01-0.1 microM) produced primarily apoptosis, but higher concentrations were associated with cellular lactate dehydrogenase efflux and necrosis. TMT increased generation of cellular reactive oxygen species, which was inhibited by either L-NAME (inhibitor of nitric oxide synthase, NOS) or catalase, indicating that both NO and H(2)O(2) are formed on TMT exposure. Since chelerythrine (selective PKC inhibitor) also inhibited oxidative species generation, PKC appears to play a significant role in TMT-induced oxidative stress. The metabotropic glutamate receptor antagonist, MCPG, (but not MK-801) prevented oxidative species generation, indicating significant involvement of metabotropic receptors (but not NMDA receptors) in TMT-induced oxidative stress. NOS involvement in the action of TMT was confirmed through measurement of nitrite, which increased concentration dependently. Nitrite accumulation was blocked by L-NAME, chelerythrine, or MCPG, showing that NO is generated by TMT and that associated ch...Continue Reading

References

Jun 1, 1979·Analytical Biochemistry·H OhkawaK Yagi
Jan 1, 1992·Neuron·D S Bredt, S H Snyder
Dec 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·L J IgnarroG Chaudhuri
Jun 1, 1987·Neurology·R BesserH C Hopf
Feb 1, 1986·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·L W Chang
Jul 1, 1984·Neuropathology and Applied Neurobiology·A W BrownW N Aldridge
Nov 1, 1995·Journal of Neurochemistry·G PavlakovićG E Isom
Feb 1, 1995·Free Radical Biology & Medicine·S J Stohs, D Bagchi
Dec 11, 1994·Nucleic Acids Research·M HerrmannJ R Kalden
Sep 1, 1995·Journal of Neuroscience Methods·P G GunasekarG E Isom
May 23, 1998·Annual Review of Pharmacology and Toxicology·L G Costa
Jul 7, 1998·Toxicology and Applied Pharmacology·B VivianiM Marinovich
Oct 21, 1998·Developmental Neuroscience·G D ZeevalkW J Nicklas
Feb 11, 2000·Toxicologic Pathology·M A PhilbertK R Reuhl

❮ Previous
Next ❯

Citations

Jul 25, 2009·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Fernando PorcelliGianluigi Veglia
Nov 12, 2010·Cell Biology and Toxicology·Armando Varela-RamirezRenato J Aguilera
Aug 9, 2002·Biochemical Pharmacology·Cecilie Resen-Fellie SkarningHarald Osmundsen
Mar 26, 2003·Brain Research. Molecular Brain Research·Jae-Ho YangPrasada Rao S Kodavanti
Aug 23, 2011·Toxicology and Applied Pharmacology·Hilary Afeseh NgwaAnumantha G Kanthasamy
Mar 19, 2011·Neurochemistry International·Maria Concetta GelosoFabrizio Michetti
May 27, 2008·Brain Research Bulletin·K PrabhakaranP G Gunasekar
Jan 15, 2008·Neurochemistry International·Francesco MisitiFabrizio Michetti
Jun 15, 2007·Toxicology in Vitro : an International Journal Published in Association with BIBRA·E K WoehrlingM D Coleman
Jul 6, 2006·The Journal of Veterinary Medical Science·Wu DongTakeo Hiraga
Dec 13, 2012·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Alessandra PagliaraniVittoria Ventrella
May 5, 2016·Journal of Applied Toxicology : JAT·Zhi-Bin TongDavid Gerhold
Apr 17, 2003·Experimental Brain Research·Michael J HaasArshag D Mooradian
Sep 7, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Gennaro GiordanoLucio G Costa
May 17, 2018·Drug and Chemical Toxicology·Samaneh SilakhoriSoghra Mehri
Apr 2, 2019·Journal of Cellular Physiology·Mansoureh SoleimaniFereshteh Azedi
Dec 29, 2019·International Journal of Molecular Sciences·Sabrina CeccarigliaCarlo Gangitano
Oct 8, 2009·Alternatives to Laboratory Animals : ATLA·Robert A Smith
Aug 7, 2009·Chemical Research in Toxicology·Jiali CaiZhenghong Zuo

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis