+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Inhibition of sonic hedgehog signaling aggravates brain damage associated with the down-regulation of Gli1, Ptch1 and SOD1 expression in acute ischemic stroke



Inhibition of sonic hedgehog signaling aggravates brain damage associated with the down-regulation of Gli1, Ptch1 and SOD1 expression in acute ischemic stroke



Neuroscience Letters 506(1): 1-6



Oxidative and cytotoxic damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Recent studies have indicated that sonic hedgehog (Shh) signaling could protect neurons against oxidative stress by increasing superoxide dismutase 1 (SOD1) activity. Glioma-associated oncogene homolog 1 (Gli1) and patched-1 (Ptch1) are both components and transcriptional targets of the Shh pathway. Here, we designed this study to determine the effect of inhibition of Shh pathway on the development of cerebral ischemia injury. Male, Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (pMCAO). Cyclopamine (0.18mg/kg), the classical inhibitor of Shh signaling, was stereotactic injected into the lateral cerebral ventricle immediately after pMCAO. At 24h neurological deficit was evaluated using a modified six point scale; brain water content was measured; infarct size was analyzed with 2,3,5-triphenyltetrazolium chloride (TTC). Immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), Western Blotting and activity assay were used to analyze the expression of Gli1, Ptch1 and SOD1. Compared with Vehicle group, cyclopamine down-regulated Gli1, Ptch1 and SOD1 in pMCAO-affected brain tissue (P<0.05), and increased infarct volume (P<0.05), brain water content (P<0.05) and behavioral deficits (P<0.05). Collectively, the present results suggest that inhibition of Shh signaling pathway exacerbated rat ischemic damage caused by pMCAO, which may be correlated with down-regulated expression of Gli1, Ptch1 and SOD1.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 036268464

Download citation: RISBibTeXText

PMID: 22133807

DOI: 10.1016/j.neulet.2011.11.027


Related references

Immunohistochemical evaluation of Sonic Hedgehog signaling pathway proteins (Shh, Ptch1, Ptch2, Smo, Gli1, Gli2, and Gli3) in sporadic and syndromic odontogenic keratocysts. Clinical Oral Investigations 23(1): 153-159, 2019

Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma. Bmc Cancer 10: 614, 2010

Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Proceedings of the National Academy of Sciences of the United States of America 101(34): 12561-6, 2004

The sonic hedgehog-GLI1 signaling pathway in brain tumor development. Expert Opinion on Therapeutic Targets 16(12): 1227-1238, 2012

Polydatin modulates inflammation by decreasing NF-κB activation and oxidative stress by increasing Gli1, Ptch1, SOD1 expression and ameliorates blood-brain barrier permeability for its neuroprotective effect in pMCAO rat brain. Brain Research Bulletin 87(1): 50-59, 2012

Sonic Hedgehog/GLI₁ signaling pathway inhibition restricts cell migration and invasion in human gliomas. Neurological Research 32(9): 975-980, 2010

Sonic hedgehog signaling activates stromal Gli1 expression and accelerates prostate cancer xenograft tumor growth. Developmental Biology 247(2): 478, 2002

The Neuroprotective Roles of Sonic Hedgehog Signaling Pathway in Ischemic Stroke. Neurochemical Research 43(12): 2199-2211, 2018

DeSUMOylation of Gli1 by SENP1 Attenuates Sonic Hedgehog Signaling. Molecular and Cellular Biology 37(18):, 2017

Anticancer drugs and the regulation of Hedgehog genes GLI1 and PTCH1, a comparative study in nonmelanoma skin cancer cell lines. Anti-Cancer Drugs 28(10): 1106-1117, 2017

Empowering sonic hedgehog to rescue brain cells after ischemic stroke. Neural Regeneration Research 10(3): 360-362, 2015

Synergism between Hedgehog-GLI and EGFR signaling in Hedgehog-responsive human medulloblastoma cells induces downregulation of canonical Hedgehog-target genes and stabilized expression of GLI1. Plos one 8(6): E65403, 2013

Resveratrol Pretreatment Decreases Ischemic Injury and Improves Neurological Function Via Sonic Hedgehog Signaling After Stroke in Rats. Molecular Neurobiology 54(1): 212-226, 2017

Sonic Hedgehog-Gli1 signaling pathway might become an effective therapeutic target in gastrointestinal neuroendocrine carcinomas. Cancer Biology and Therapy 5(11): 1530-1538, 2006

Discovery of sonic hedgehog expression in postnatal growth plate chondrocytes: differential regulation of sonic and Indian hedgehog by retinoic acid. Journal of Cellular Biochemistry 87(2): 173-187, 2002