PMID- 11273003
OWN - NLM
STAT- MEDLINE
DCOM- 20010329
LR  - 20190513
IS  - 0022-3069 (Print)
IS  - 0022-3069 (Linking)
VI  - 60
IP  - 2
DP  - 2001 Feb
TI  - Insulin-like growth factor-I and over-expression of Bcl-xL prevent 
      glucose-mediated apoptosis in Schwann cells.
PG  - 147-60
AB  - Schwann cells (SCs), the myelinating cells of the peripheral nervous system, are 
      lost or damaged in patients suffering from diabetic neuropathy. In the current 
      study, 2 model systems are used to study the mechanism of SC damage in diabetic 
      neuropathy: the streptozotocin (STZ)-treated diabetic rat and cultures of 
      purified SCs in vitro. Electron microscopy of dorsal root ganglia from 
      STZ-treated rats reveals classic ultrastructural features of apoptosis in SCs, 
      including chromatin clumping and prominent vacuolation. Bisbenzamide staining of 
      SCs cultured in hyperglycemic defined media shows nuclear blebbing of apoptotic 
      cells. Insulin-like growth factor-I (IGF-I) is protective. LY294002, a 
      phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, blocks the effect of 
      IGF-I. High glucose induces caspase cleavage in apoptotic SCs--an effect that is 
      blocked by bok-asp-fmk (BAF), a caspase inhibitor. Although Bcl-xL expression 
      remains unchanged in experimental conditions, over-expression of Bcl-xL protects 
      SCs from apoptosis. In summary, hyperglycemia induces caspase activation and 
      morphologic changes in SCs consistent with apoptotic death, both in vivo and in 
      vitro. Over-expression of Bcl-xL, or IGF-I, signaling via PI 3-kinase, protects 
      SCs from glucose-mediated apoptosis in vitro. IGF-I may be useful in preventing 
      hyperglycemia-induced damage to SCs in patients suffering from diabetic 
      neuropathy.
FAU - Delaney, C L
AU  - Delaney CL
AD  - Department of Neurology, University of Michigan, Ann Arbor, USA.
FAU - Russell, J W
AU  - Russell JW
FAU - Cheng, H L
AU  - Cheng HL
FAU - Feldman, E L
AU  - Feldman EL
LA  - eng
GR  - NS01938/NS/NINDS NIH HHS/United States
GR  - R01 NS 36778/NS/NINDS NIH HHS/United States
GR  - T32NS07222-17/NS/NINDS NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (Bcl2l1 protein, rat)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-X Protein)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - IY9XDZ35W2 (Glucose)
RN  - LHQ7J5KV9B (Bisbenzimidazole)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Bisbenzimidazole
MH  - Diabetic Neuropathies/*metabolism/*pathology
MH  - Ganglia, Spinal/metabolism/pathology
MH  - Glucose/metabolism/pharmacology
MH  - Insulin-Like Growth Factor I/*metabolism
MH  - Male
MH  - Microscopy, Electron
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Schwann Cells/*metabolism/*pathology/ultrastructure
MH  - bcl-X Protein
EDAT- 2001/03/29 10:00
MHDA- 2001/04/03 10:01
CRDT- 2001/03/29 10:00
PHST- 2001/03/29 10:00 [pubmed]
PHST- 2001/04/03 10:01 [medline]
PHST- 2001/03/29 10:00 [entrez]
AID - 10.1093/jnen/60.2.147 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2001 Feb;60(2):147-60. doi: 10.1093/jnen/60.2.147.