PMID- 14679058
OWN - NLM
STAT- MEDLINE
DCOM- 20040116
LR  - 20190616
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 1005
DP  - 2003 Nov
TI  - Immunolocalization of caspase-3 in pancreatic islets of NOD mice during 
      cyclophosphamide-accelerated diabetes.
PG  - 192-5
AB  - Apoptosis may be a major mechanism of beta cell loss during insulin-dependent 
      diabetes mellitus. Caspase-3 is a key enzyme involved in the terminal steps of 
      this death process. Here, the intra-islet expression of caspase-3 in the NOD 
      mouse was examined immunohistochemically following acceleration of the disease 
      with cyclophosphamide. Female NOD mice were treated at day 95 with 
      cyclophosphamide, and caspase-3 expression in pancreatic sections was studied at 
      days 0, 4, 7, 11, and 14 and compared with age-matched control tissue. In the 
      treated group at day 0, caspase-3 labeling was seen in several peri-islet 
      macrophages and only extremely rarely in beta cells. At day 4, only a few beta 
      cells weakly expressed the enzyme. From day 7, caspase-3 expression began to 
      increase in intra-islet macrophages and reached a peak at days 11 and 14, when a 
      small number of CD4 and CD8 T cells also showed positive labeling. Beta cell 
      expression of caspase-3 at days 11 and 14 was rare. At this stage, several 
      intra-islet immune cells with positive labeling for the enzyme coexpressed either 
      Fas or interleukin-1beta. Only a small proportion of intra-islet caspase-3 cells 
      showed apoptotic nuclei judged by terminal deoxynucleotidyl transferase-mediated 
      dUTP nick end labeling (TUNEL). We conclude that, during 
      cyclophosphamide-accelerated diabetes, the predominant caspase-3 immunolabeling 
      in intra- and extra-islet macrophages suggests that apoptosis of macrophages may 
      be an important mechanism for their elimination. The virtual absence of caspase-3 
      immunolabeling in most beta cells even during the height of beta cell loss 
      supports the need for developing other markers of early beta cell apoptosis in 
      the NOD mouse.
FAU - Reddy, Shiva
AU  - Reddy S
AD  - School of Biological Sciences, Department of Pediatrics, University of Auckland, 
      Auckland, New Zealand. s.reddy@auckland.ac.nz
FAU - Bradley, Joshua
AU  - Bradley J
FAU - Ross, Jacqueline M
AU  - Ross JM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Caspase 3
MH  - Caspases/*metabolism
MH  - Cyclophosphamide/*pharmacology
MH  - Diabetes Mellitus, Type 1/chemically induced/*enzymology
MH  - Female
MH  - Immunohistochemistry
MH  - Islets of Langerhans/*enzymology
MH  - Mice
MH  - Mice, Inbred NOD
EDAT- 2003/12/18 05:00
MHDA- 2004/01/17 05:00
CRDT- 2003/12/18 05:00
PHST- 2003/12/18 05:00 [pubmed]
PHST- 2004/01/17 05:00 [medline]
PHST- 2003/12/18 05:00 [entrez]
AID - 10.1196/annals.1288.025 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2003 Nov;1005:192-5. doi: 10.1196/annals.1288.025.