Critical role of lysosome and its associated protein cathepsin D in manganese-induced toxicity in cultured midbrain astrocyte

Neurochemistry International
Xiaolan FanWeidong Le

Abstract

Astrocyte is considered to be the initial target in manganese neurotoxicity; however, the ultra structure changes in the cells and the mechanism underlying the manganese-induced toxicity are still unclear. In this study, we conducted several assays in cultured midbrain astrocyte to determine the role of mitochondria, lysosome and its associated protein cathepsin D in the manganese-induced toxicity. We found that a mixed form of cell death in the manganese treated astrocyte. During the process of cell death, we detected extensive cytoplasmic vacuolation, mitochondrial swelling, and increased number and membrane permeability of lysosomes in the manganese treated astrocyte. Furthermore, we documented that after exposed to manganese, the Bax protein level in the astrocyte was increased, and its cellular distribution was significantly translocated from cytosol to mitochondria and lysosomes. Moreover, we demonstrated that manganese treatment caused significant increase of lysosomal enzyme cathepsin D, and pretreatment with cathepsin D inhibitor pepstatin A increased the apoptotic cell death. Collectively, our study suggests that different forms of cell death are involved in manganese-induced toxicity in the cultured midbrain astrocyt...Continue Reading

References

Feb 1, 1992·Journal of Neurochemistry·M AschnerH K Kimelberg
Apr 1, 1987·Neurochemical Research·M Banay-SchwartzA Lajtha
Dec 1, 1983·Toxicology and Applied Pharmacology·H SuzukiT Ono
Jan 13, 1998·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·M S DesoleE Miele
Mar 27, 1999·Environmental Research·M Aschner
Jun 1, 2000·Toxicological Sciences : an Official Journal of the Society of Toxicology·J Henriksson, H Tjälve
Feb 28, 2002·Free Radical Biology & Medicine·Sang-Hyun ChoiBoe-Gwun Chun
May 16, 2002·Experimental Neurology·Chun-Jung Chen, Su-Lan Liao
Jul 11, 2002·Brain Research. Molecular Brain Research·Mayka Tomás-CamardielAlberto Machado
Jul 11, 2002·Neurochemistry International·Alan S Hazell
Jul 11, 2002·The American Journal of Pathology·Karin RobergKarin Ollinger
Nov 12, 2002·Environmental Health Perspectives·Robert A Yokel
Nov 7, 2003·Glia·Josep SauraJoan Serratosa
Jun 3, 2004·The Journal of Biological Chemistry·Kakulavarapu V Rama Rao, Michael D Norenberg
Dec 21, 2004·The Journal of Pharmacology and Experimental Therapeutics·Calivarathan LatchoumycandaneAnumantha G Kanthasamy
Jul 16, 2005·Cell Death and Differentiation·H JiangJ Schacht
Sep 30, 2005·International Journal of Experimental Pathology·Katarina KågedalKarin Ollinger
Apr 6, 2007·Neurotoxicology·K V Rama RaoM D Norenberg
May 1, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Dejan MilatovicMichael Aschner
Aug 30, 2007·Proceedings of the National Academy of Sciences of the United States of America·Masaaki KomatsuZhenyu Yue
Mar 4, 2008·Brain Research·Zhaoobao YinMichael Aschner
Jun 21, 2008·Carcinogenesis·Vitalia SagulenkoFrank Westermann
Jul 17, 2008·Autophagy·Nicolas PalletDany Anglicheau
Jul 29, 2008·Journal of Cellular and Molecular Medicine·Roberta CastinoCiro Isidoro
May 22, 2009·Journal of Neurochemistry·Gregg D StanwoodBethAnn McLaughlin
Apr 23, 2011·American Journal of Physiology. Gastrointestinal and Liver Physiology·Yuji IwashitaEugene B Chang

❮ Previous
Next ❯

Citations

Apr 29, 2015·Biochimica Et Biophysica Acta·Débora E RinaldiFelicitas de Tezanos Pinto
Jan 30, 2016·Environmental Health Perspectives·Tongjian CaiJingyuan Chen

❮ Previous
Next ❯

Related Concepts

Related Feeds

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.

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

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.