Oxidative Stress and Programmed Cell Death in Diabetic Neuropathy
dc.contributor.author | Vincent, Andrea M. | en_US |
dc.contributor.author | Brownlee, Michael | en_US |
dc.contributor.author | Russell, James W. | en_US |
dc.date.accessioned | 2010-06-01T21:00:13Z | |
dc.date.available | 2010-06-01T21:00:13Z | |
dc.date.issued | 2002-04 | en_US |
dc.identifier.citation | VINCENT, ANDREA M.; BROWNLEE, MICHAEL; RUSSELL, JAMES W. (2002). "Oxidative Stress and Programmed Cell Death in Diabetic Neuropathy." Annals of the New York Academy of Sciences 959(1 Increasing Healthy Life Span: Conventional Measures and Slowing the Innate Aging Process ): 368-383. <http://hdl.handle.net/2027.42/74096> | en_US |
dc.identifier.issn | 0077-8923 | en_US |
dc.identifier.issn | 1749-6632 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/74096 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=11976211&dopt=citation | en_US |
dc.description.abstract | Recent evidence in both animal models and human sural nerve biopsies indicates an association with oxidative stress, mitochondrial (Mt) membrane depolarization (MMD), and induction of programmed cell death (PCD). In streptozotocin (STZ)-treated diabetic rats, hyperglycemia induces typical apoptotic changes as well as swelling and disruption of the Mt cristae in diabetic dorsal root ganglion neurons (DRG) and Schwann cells (SC), but these changes are only rarely observed in control neurons. In human sural nerve biopsies, from patients with diabetic sensory neuropathy, there is transmission electromicrograph evidence of swelling and disruption of the Mt and cristae compared to patients without peripheral neuropathy. In human SH-SY5Y neurons, rat sensory neurons, and SC, in vivo , there is an increase in reactive oxygen species (ROS) after exposure to 20 mM added glucose. In parallel, there is an initial Mt membrane hyperpolarization followed by depolarization (MMD). In turn, MMD is coupled with cleavage of caspases. Various strategies aimed at inhibiting the oxidative burst, or stabilizing the ΔΨ M , block induction of PCD. First, growth factors such as NGF can block induction of ROS and/or stabilize the ΔΨ M . This, in turn, is associated with inhibition of PCD. Second, reduction of ROS generation in neuronal Mt prevents neuronal PCD. Third, up-regulation of uncoupling proteins (UCPs), which stabilize the ΔΨ M , blocks induction of caspase cleavage. Collectively, these findings indicate that hyperglycemic conditions observed in diabetes mellitus are associated with oxidative stress-induced neuronal and SC death, and targeted therapies aimed at regulating ROS may prove effective in therapy of diabetic neuropathy. | en_US |
dc.format.extent | 10742582 bytes | |
dc.format.extent | 3109 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Blackwell Publishing Ltd | en_US |
dc.rights | 2002 New York Academy of Sciences | en_US |
dc.subject.other | Oxidative Stress | en_US |
dc.subject.other | Diabetes | en_US |
dc.subject.other | Apoptosis | en_US |
dc.subject.other | Mitochondria | en_US |
dc.subject.other | Neuropathy | en_US |
dc.title | Oxidative Stress and Programmed Cell Death in Diabetic Neuropathy | en_US |
dc.type | Article | en_US |
dc.subject.hlbsecondlevel | Science (General) | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Neurology, University of Michigan, Ann Arbor, Michigan 48109, USA | en_US |
dc.contributor.affiliationother | Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA | en_US |
dc.identifier.pmid | 11976211 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/74096/1/j.1749-6632.2002.tb02108.x.pdf | |
dc.identifier.doi | 10.1111/j.1749-6632.2002.tb02108.x | en_US |
dc.identifier.source | Annals of the New York Academy of Sciences | en_US |
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dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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