PMID- 20825413
OWN - NLM
STAT- MEDLINE
DCOM- 20110318
LR  - 20211020
IS  - 1750-3639 (Electronic)
IS  - 1015-6305 (Print)
IS  - 1015-6305 (Linking)
VI  - 21
IP  - 1
DP  - 2011 Jan
TI  - Role of cytotoxic protease granzyme-b in neuronal degeneration during human 
      stroke.
PG  - 16-30
LID - 10.1111/j.1750-3639.2010.00426.x [doi]
AB  - Infiltration of leukocytes into post-ischemic cerebrum is a well-described 
      phenomenon in stroke injury. Because CD-8(+) T-lymphocytes secrete cytotoxic 
      proteases, including granzyme-b (Gra-b) that exacerbates post-ischemic brain 
      damage, we investigated roles of Gra-b in human stroke. To study the role of 
      Gra-b in stroke, ischemic and non-ischemic tissues (from post-mortem stroke 
      patients) were analyzed using immunoblotting, co-immunoprecipitation, terminal 
      deoxy uridine nick end labeling (TUNEL) and Annexin-V immunostaining, and in 
      vitro neuron survival assays. Activated CG-SH cells and supernatants were used to 
      model leukocyte-dependent injury. Non-ischemic brain tissues were used as 
      non-pathological controls. Non-activated CG-SH cells and supernatants were used 
      as controls for in vitro experiments. Human stroke (ischemic) samples contained 
      significantly higher levels of Gra-b and interferon-gamma inducible protein-10 
      (IP-10/CXCL10) than non-ischemic controls. In stroke, poly (ADP-ribose) 
      polymerase-1 and heat shock protein-70 were cleaved to canonical proteolytic 
      "signature" fragments by Gra-b. Gra-b was also found to bind to Bid and 
      caspase-3. Gra-b also co-localized with Annexin-V(+) /TUNEL(+) in degenerating 
      neurons. Importantly, Gra-b inhibition protected both normal and 
      ischemia-reperfused neurons against in vitro neurotoxicity mediated by activated 
      CG-SH cells and supernatants. These results suggest that increased leukocyte 
      infiltration and elevated Gra-b levels in the post-stroke brain can induce 
      contact-dependent and independent post-ischemic neuronal death to aggravate 
      stroke injury.
CI  - (c) 2010 The Authors; Brain Pathology (c) 2010 International Society of 
      Neuropathology.
FAU - Chaitanya, Ganta Vijay
AU  - Chaitanya GV
AD  - Department of Molecular and Cellular Physiology, School of Medicine, 
      Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, 
      Shreveport, La, USA.
FAU - Eeka, Prabhakar
AU  - Eeka P
FAU - Munker, Reinhold
AU  - Munker R
FAU - Alexander, Jonathan Steven
AU  - Alexander JS
FAU - Babu, Phanithi Prakash
AU  - Babu PP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Brain Pathol
JT  - Brain pathology (Zurich, Switzerland)
JID - 9216781
RN  - 0 (CXCL10 protein, human)
RN  - 0 (Chemokine CXCL10)
RN  - EC 3.4.21.- (Granzymes)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Analysis of Variance
MH  - Apoptosis
MH  - Blotting, Western
MH  - Brain/*metabolism/pathology
MH  - Brain Ischemia/*metabolism/pathology
MH  - Caspase 3/metabolism
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Chemokine CXCL10/metabolism
MH  - Female
MH  - Granzymes/*metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Immunoprecipitation
MH  - In Situ Nick-End Labeling
MH  - Male
MH  - Middle Aged
MH  - Necrosis
MH  - Nerve Degeneration/*metabolism/pathology
MH  - Neurons/metabolism/pathology
MH  - Stroke/*metabolism/pathology
PMC - PMC8094313
COIS- The authors declare no conflict of interest.
EDAT- 2010/09/10 06:00
MHDA- 2011/03/19 06:00
PMCR- 2010/12/03
CRDT- 2010/09/10 06:00
PHST- 2010/09/10 06:00 [entrez]
PHST- 2010/09/10 06:00 [pubmed]
PHST- 2011/03/19 06:00 [medline]
PHST- 2010/12/03 00:00 [pmc-release]
AID - BPA426 [pii]
AID - 10.1111/j.1750-3639.2010.00426.x [doi]
PST - ppublish
SO  - Brain Pathol. 2011 Jan;21(1):16-30. doi: 10.1111/j.1750-3639.2010.00426.x.