Oxidative stress and programmed cell death in diabetic neuropathy

Andrea M. Vincent, Michael Brownlee, James W. Russell

Research output: Contribution to journalArticle

227 Citations (Scopus)

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 (RES) 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 ΔΨM, block induction of PCD. First, growth factors such as NGF can block induction of Res and/or stabilize the ΔΨM. This, in turn, is associated with inhibition of PCD. Second, reduction of Res generation in neuronal Mt prevents neuronal PCD. Third, up-regulation of uncoupling proteins (UCPs), which stabilize the ΔΨM, 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 Res may prove effective in therapy of diabetic neuropathy.

Original languageEnglish (US)
Pages (from-to)368-383
Number of pages16
JournalAnnals of the New York Academy of Sciences
Volume959
StatePublished - 2002

Fingerprint

Oxidative stress
Diabetic Neuropathies
Cell death
Depolarization
Oxidative Stress
Cell Death
Neurons
Schwann Cells
Mitochondrial Swelling
Membranes
Sural Nerve
Biopsy
Mitochondrial Membranes
Caspases
Swelling
Rats
Respiratory Burst
Spinal Ganglia
Peripheral Nervous System Diseases
Nerve Growth Factor

Keywords

  • Apoptosis
  • Diabetes
  • Mitochondria
  • Neuropathy
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Vincent, A. M., Brownlee, M., & Russell, J. W. (2002). Oxidative stress and programmed cell death in diabetic neuropathy. Annals of the New York Academy of Sciences, 959, 368-383.

Oxidative stress and programmed cell death in diabetic neuropathy. / Vincent, Andrea M.; Brownlee, Michael; Russell, James W.

In: Annals of the New York Academy of Sciences, Vol. 959, 2002, p. 368-383.

Research output: Contribution to journalArticle

Vincent, AM, Brownlee, M & Russell, JW 2002, 'Oxidative stress and programmed cell death in diabetic neuropathy', Annals of the New York Academy of Sciences, vol. 959, pp. 368-383.
Vincent, Andrea M. ; Brownlee, Michael ; Russell, James W. / Oxidative stress and programmed cell death in diabetic neuropathy. In: Annals of the New York Academy of Sciences. 2002 ; Vol. 959. pp. 368-383.
@article{a8783d46bc194b228f1cc83c9daedbf4,
title = "Oxidative stress and programmed cell death in diabetic neuropathy",
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 (RES) 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 ΔΨM, block induction of PCD. First, growth factors such as NGF can block induction of Res and/or stabilize the ΔΨM. This, in turn, is associated with inhibition of PCD. Second, reduction of Res generation in neuronal Mt prevents neuronal PCD. Third, up-regulation of uncoupling proteins (UCPs), which stabilize the ΔΨM, 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 Res may prove effective in therapy of diabetic neuropathy.",
keywords = "Apoptosis, Diabetes, Mitochondria, Neuropathy, Oxidative stress",
author = "Vincent, {Andrea M.} and Michael Brownlee and Russell, {James W.}",
year = "2002",
language = "English (US)",
volume = "959",
pages = "368--383",
journal = "Annals of the New York Academy of Sciences",
issn = "0077-8923",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Oxidative stress and programmed cell death in diabetic neuropathy

AU - Vincent, Andrea M.

AU - Brownlee, Michael

AU - Russell, James W.

PY - 2002

Y1 - 2002

N2 - 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 (RES) 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 ΔΨM, block induction of PCD. First, growth factors such as NGF can block induction of Res and/or stabilize the ΔΨM. This, in turn, is associated with inhibition of PCD. Second, reduction of Res generation in neuronal Mt prevents neuronal PCD. Third, up-regulation of uncoupling proteins (UCPs), which stabilize the ΔΨM, 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 Res may prove effective in therapy of diabetic neuropathy.

AB - 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 (RES) 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 ΔΨM, block induction of PCD. First, growth factors such as NGF can block induction of Res and/or stabilize the ΔΨM. This, in turn, is associated with inhibition of PCD. Second, reduction of Res generation in neuronal Mt prevents neuronal PCD. Third, up-regulation of uncoupling proteins (UCPs), which stabilize the ΔΨM, 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 Res may prove effective in therapy of diabetic neuropathy.

KW - Apoptosis

KW - Diabetes

KW - Mitochondria

KW - Neuropathy

KW - Oxidative stress

UR - http://www.scopus.com/inward/record.url?scp=0036238441&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036238441&partnerID=8YFLogxK

M3 - Article

C2 - 11976211

AN - SCOPUS:0036238441

VL - 959

SP - 368

EP - 383

JO - Annals of the New York Academy of Sciences

JF - Annals of the New York Academy of Sciences

SN - 0077-8923

ER -