Oxidative Stress and Programmed Cell Death in Diabetic Neuropathy
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
No Canadian affiliation. An affiliation-only frame — the usual design — would never have seen this work. It is one of the works that make the case for inverting the frame.
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
- Teacher spread
- 0.227 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
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 DeltaPsi(M), block induction of PCD. First, growth factors such as NGF can block induction of ROS and/or stabilize the DeltaPsi(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 DeltaPsi(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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
The record
- Venue
- Annals of the New York Academy of Sciences
- Topic
- Pain Mechanisms and Treatments
- Field
- Medicine
- Canadian institutions
- —
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin DiseasesNIH Clinical CenterNational Cancer InstituteNational Institutes of HealthNational Institute of Diabetes and Digestive and Kidney DiseasesUniversity of CalgaryNational Institute of Neurological Disorders and StrokeGeriatric Research Education and Clinical CenterUniversity of Michigan
- Keywords
- Oxidative stressDepolarizationDorsal root ganglionProgrammed cell deathMitochondrionReactive oxygen speciesCell biologyApoptosisStreptozotocinEndocrinologyInternal medicineMedicineChemistryPharmacologyDiabetes mellitusBiologyNeuroscienceBiochemistrySensory system
- Has abstract in OpenAlex
- yes