PMID- 11320180
OWN - NLM
STAT- MEDLINE
DCOM- 20010524
LR  - 20211231
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 56
IP  - 8
DP  - 2001 Apr 24
TI  - Lack of apoptosis in mitochondrial encephalomyopathies.
PG  - 1070-4
AB  - BACKGROUND/OBJECTIVE: Apoptosis, or programmed cell death, is an evolutionary 
      conserved mechanism essential for morphogenesis and tissue homeostasis, but it 
      plays an important role also in pathologic conditions, including neurologic 
      disorders. Its execution pathway is critically regulated at the mitochondrial 
      level. Evidence of apoptosis in muscle specimens was investigated in patients 
      with genetically defined mitochondrial encephalomyopathies. METHODS: Thirty-three 
      muscle biopsies from patients with genotypically different mitochondrial diseases 
      (single and multiple deletions, A3243G/A8344G point mutations of the 
      mitochondrial DNA) were studied. The terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) reaction was used as a marker 
      of nuclear DNA fragmentation, as well as antibodies against pro- (Fas) or anti- 
      (Bcl-2) apoptotic factors. Also, because one hallmark of apoptosis is 
      morphologic, ultrastructural studies were performed on skeletal muscle from 18 of 
      33 patients, examining both phenotypically normal and ragged red fibers. RESULTS: 
      In all muscle biopsies, no significant expression of either pro (Fas) and 
      inhibiting (Bcl-2) apoptosis-related proteins was found, nor TUNEL positivity. 
      This latter finding is confirmed by lack of morphologic evidence of apoptosis in 
      all the fibers examined at the ultrastructural level. CONCLUSION: The authors' 
      findings suggest that genetically determined defects of oxidative phosphorylation 
      do not induce the apoptotic process and that apoptosis is not involved in the 
      pathogenesis of mitochondrial disorders.
FAU - Sciacco, M
AU  - Sciacco M
AD  - Centro Dino Ferrari, Istituto di Clinica Neurologica, University of Milan, 
      Ospedale Maggiore IRCCS, Milan, Italy.
FAU - Fagiolari, G
AU  - Fagiolari G
FAU - Lamperti, C
AU  - Lamperti C
FAU - Messina, S
AU  - Messina S
FAU - Bazzi, P
AU  - Bazzi P
FAU - Napoli, L
AU  - Napoli L
FAU - Chiveri, L
AU  - Chiveri L
FAU - Prelle, A
AU  - Prelle A
FAU - Comi, G P
AU  - Comi GP
FAU - Bresolin, N
AU  - Bresolin N
FAU - Scarlato, G
AU  - Scarlato G
FAU - Moggio, M
AU  - Moggio M
LA  - eng
GR  - 1001/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (BCL2L11 protein, human)
RN  - 0 (Bcl-2-Like Protein 11)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Membrane Proteins)
RN  - 0 (Oligopeptides)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (valyl-glutamyl-isoleucyl-asparaginyl-cysteinyl-threonyl-arginine)
SB  - IM
MH  - Apoptosis/physiology
MH  - Apoptosis Regulatory Proteins
MH  - Bcl-2-Like Protein 11
MH  - Carrier Proteins/metabolism
MH  - DNA Fragmentation/*physiology
MH  - DNA, Mitochondrial/*physiology
MH  - Humans
MH  - *Membrane Proteins
MH  - Mitochondrial Encephalomyopathies/genetics/*metabolism
MH  - Muscle Fibers, Fast-Twitch/*metabolism/ultrastructure
MH  - Mutation/genetics/*physiology
MH  - Oligopeptides/metabolism
MH  - *Proto-Oncogene Proteins
EDAT- 2001/04/26 10:00
MHDA- 2001/05/26 10:01
CRDT- 2001/04/26 10:00
PHST- 2001/04/26 10:00 [pubmed]
PHST- 2001/05/26 10:01 [medline]
PHST- 2001/04/26 10:00 [entrez]
AID - 10.1212/wnl.56.8.1070 [doi]
PST - ppublish
SO  - Neurology. 2001 Apr 24;56(8):1070-4. doi: 10.1212/wnl.56.8.1070.