RGD Reference Report - A purine antimetabolite attenuates toll-like receptor-2, -4, and subarachnoid hemorrhage-induced brain apoptosis. - Rat Genome Database

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A purine antimetabolite attenuates toll-like receptor-2, -4, and subarachnoid hemorrhage-induced brain apoptosis.

Authors: Chang, Chih-Zen  Wu, Shu-Chuan  Kwan, Aij-Lie 
Citation: Chang CZ, etal., J Surg Res. 2015 Dec;199(2):676-87. doi: 10.1016/j.jss.2015.06.011. Epub 2015 Jun 12.
RGD ID: 13782347
Pubmed: PMID:26163325   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jss.2015.06.011   (Journal Full-text)


BACKGROUND: Upregulation of high-level toll-like receptors (TLRs) is observed in the serum of animals following experimental subarachnoid hemorrhage (SAH) and is highly related to SAH-induced early brain injury (EBI). The present study was of interest to examine the effect of 6-mercaptopurine (6-MP) on alternation of TLR-2, -3, and -4 in this model.
METHODS: A rodent SAH model was used. Administration with 6-MP (0.5/1/2 mg/kg/d) was initiated 1 h after the induction of SAH via an osmotic minipump. Cerebral cortex was harvested to measure TLRs messenger RNA and protein (reverse transcription polymerase chain reaction [rt-PCR] and Western blot). Cerebral cortex was harvested for activated caspases (rt-PCR) measurement.
RESULTS: Cellular evaluation revealed increased neuronal nuclei(+) neurons with vacuolated nuclear and glial fibrillary acidic protein(+) astrocytes in the SAH group, but absent in the 6-MP treatment and healthy controls. The TLR-3 levels were not significantly increased in animals subject to SAH, compared with the controls (no SAH). The levels of TLR-2 and -4 in the SAH only and SAH plus vehicle groups were significantly elevated (P < 0.01), and treatment with 6-MP reduced TLR-2, -3 (at 2 mg/kg), and -4 (dose-dependently) protein expression following SAH. Likewise, the TLR-4 messenger RNA levels were also significantly reduced in the 6-MP (at 1 mg/kg and 2 mg/kg) groups. Cleaved caspase-3 and caspase-9a were reduced at 2-mg/kg 6-MP treatment group.
CONCLUSIONS: These results show that 6-MP attenuates the expression of TLR-2, -4, especially TLR-4, which play an antiapoptotic effect on SAH-induced EBI. This finding supported that through modulating TLRs, 6-MP can attenuate SAH-induced EBI. Those results offer credit to the neuroprotective effect of 6-MP.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Bcl2  (BCL2, apoptosis regulator)
Casp3  (caspase 3)
Casp9  (caspase 9)

Genes (Mus musculus)
Bcl2  (B cell leukemia/lymphoma 2)
Casp3  (caspase 3)
Casp9  (caspase 9)

Genes (Homo sapiens)
BCL2  (BCL2 apoptosis regulator)
CASP3  (caspase 3)
CASP9  (caspase 9)


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