PMID- 24410139
OWN - NLM
STAT- MEDLINE
DCOM- 20150512
LR  - 20171116
IS  - 1563-5279 (Electronic)
IS  - 0020-7454 (Linking)
VI  - 124
IP  - 10
DP  - 2014 Oct
TI  - Minocycline mechanism of neuroprotection involves the Bcl-2 gene family in optic 
      nerve transection.
PG  - 755-61
LID - 10.3109/00207454.2013.878340 [doi]
AB  - The second-generation tetracycline, minocycline, has been shown to exhibit 
      neuroprotective therapeutic benefits in many neurodegenerative diseases including 
      experimental glaucoma and optic nerve transection (ONT). This study investigated 
      the mechanism underlying minocycline neuroprotection in a model of ONT. ONT was 
      applied unilaterally in 36 Wistar rat eyes. The rats were randomly divided into a 
      minocycline (22 mg/kg/d) treatment group and a saline treatment group (control). 
      Treatment (minocycline or saline) was given by intraperitoneal injections 
      initiated 3 d before ONT and continued daily until the end of the experiment. The 
      involvement of pro-apoptotic, pro-survival and inflammatory pathways was analyzed 
      by quantitative Real-Time Polymerase Chain Reaction at 4 h and 3 d after the 
      transection in both treatment groups. The involvement of Bcl-2 protein was 
      evaluated by immunohistochemistry. We found that Minocycline significantly 
      increased the expression of the antiapoptotic gene bcl-2 4 h after transection (n 
      = 8, p = 0.008) and decreased the expression of Bax at the same time point (n = 
      8, p = 0.03). Tumor Necrosis Factor alpha (TNFalpha), Inhibitor of Apoptosis Protein 
      (IAP1) and Gadd45alpha were significantly upregulated in the retinas of eyes with 
      ONTs compared to control (n = 10 for each gene, p = 0.02, p = 0.03, p = 0.04, 
      respectively) but this effect was unaffected by minocycline. This study further 
      support that the mechanism underlying minocycline neuroprotection involves the 
      Bcl-2 gene family, suggesting that minocycline has antiapoptotic properties that 
      support its value as a promising neuroprotective drug.
FAU - Levkovitch-Verbin, Hani
AU  - Levkovitch-Verbin H
AD  - From the Sam Rothberg Ophthalmic Molecular Biology Laboratory, Goldschleger Eye 
      Institute, Sheba Medical Center , Tel-Hashomer, Sackler Faculty of Medicine, 
      Tel-Aviv University , Israel.
FAU - Waserzoog, Yael
AU  - Waserzoog Y
FAU - Vander, Shelly
AU  - Vander S
FAU - Makarovsky, Daria
AU  - Makarovsky D
FAU - Ilia, Piven
AU  - Ilia P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140206
PL  - England
TA  - Int J Neurosci
JT  - The International journal of neuroscience
JID - 0270707
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cytokines)
RN  - 0 (Gadd45a protein, rat)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Thy-1 Antigens)
RN  - 0 (bcl-2-Associated X Protein)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 2.3.2.27 (Baculoviral IAP Repeat-Containing 3 Protein)
RN  - EC 2.3.2.27 (Birc3 protein, rat)
RN  - FYY3R43WGO (Minocycline)
SB  - IM
MH  - Animals
MH  - Baculoviral IAP Repeat-Containing 3 Protein
MH  - Cell Cycle Proteins/genetics/metabolism
MH  - Cytokines/genetics/metabolism
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/*drug effects
MH  - Inhibitor of Apoptosis Proteins/genetics/metabolism
MH  - Minocycline/*pharmacology/*therapeutic use
MH  - Neuroprotective Agents/pharmacology/therapeutic use
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Nuclear Proteins/genetics/metabolism
MH  - Optic Nerve Diseases/*drug therapy/pathology
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Retina/drug effects/metabolism/pathology
MH  - Thy-1 Antigens/metabolism
MH  - Time Factors
MH  - bcl-2-Associated X Protein/genetics/metabolism
OTO - NOTNLM
OT  - axotomy
OT  - minocycline
OT  - retinal ganglion cells
EDAT- 2014/01/15 06:00
MHDA- 2015/05/13 06:00
CRDT- 2014/01/14 06:00
PHST- 2014/01/14 06:00 [entrez]
PHST- 2014/01/15 06:00 [pubmed]
PHST- 2015/05/13 06:00 [medline]
AID - 10.3109/00207454.2013.878340 [doi]
PST - ppublish
SO  - Int J Neurosci. 2014 Oct;124(10):755-61. doi: 10.3109/00207454.2013.878340. Epub 
      2014 Feb 6.