Anti-oxidative, anti-apoptotic, and pro-angiogenic effects mediate functional improvement by sonic hedgehog against focal cerebral ischemia in rats

Huang, Shiang‐Suo; Cheng, Henrich; Tang, Ching-Min; Nien, Mao-Wei; Huang, Yuahn-Sieh; Lee, I-Huei; Yin, Jiu‐Haw; Kuo, Terry B.J.; Yang, Cheryl C.H.; Tsai, Shen‐Kou; Yang, Ding-I

doi:10.1016/j.expneurol.2013.03.004

Cited by 56 publications

(41 citation statements)

References 40 publications

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“…Several studies, including ours, reveal that manipulation of the Shh pathway carries therapeutic potential in neurodegenerative disorders and cerebral ischemia [42,43,44,45,46,47,48]. We have reported before that Shh mediates brain-derived neurotrophic factor (BDNF)-induced neuroprotection against 3-nitropropionic acid (3-NP), which is an irreversible inhibitor of mitochondrial succinate dehydrogenase, also known as Complex II in the electron respiratory chain, that has been used to investigate the molecular mechanisms concerning cell death, mitochondrial dysfunction, and neurodegeneration in Huntington’s disease (HD) [47,49].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, beneficial actions of Shh in ischemic injury have been noted [50,51,52]. By topical application of N-terminal fragment of Shh (Shh-N) and/or its specific inhibitor cyclopamine in fibrin glue over the peri-infarct cortex in the rat model of middle cerebral artery occlusion (MCAO), which mimics cerebral ischemia, we showed that Shh-N can attenuate protein oxidation and lipid peroxidation as well as increase neurogenesis and angiogenesis while decreasing astrocytosis [45]. It has also been demonstrated that, in hippocampal neurons, activation of the Shh signaling pathway may affect several features of mitochondrial function, such as increasing mitochondrial mass, inhibiting mitochondrial fission protein Drp1, and reducing mitochondrial fission while promoting mitochondrial elongation [53].…”

Section: Introductionmentioning

confidence: 99%

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Emerging Roles of Sonic Hedgehog in Adult Neurological Diseases: Neurogenesis and Beyond

Chen

Yang

Hwang

et al. 2018

IJMS

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Sonic hedgehog (Shh), a member of the hedgehog (Hh) family, was originally recognized as a morphogen possessing critical characters for neural development during embryogenesis. Recently, however, Shh has emerged as an important modulator in adult neural tissues through different mechanisms such as neurogenesis, anti-oxidation, anti-inflammation, and autophagy. Therefore, Shh may potentially have clinical application in neurodegenerative diseases and brain injuries. In this article, we present some examples, including ours, to show different aspects of Shh signaling and how Shh agonists or mimetics are used to alter the neuronal fates in various disease models, both in vitro and in vivo. Other potential mechanisms that are discussed include alteration of mitochondrial function and anti-aging effect; both are critical for age-related neurodegenerative diseases. A thorough understanding of the protective mechanisms elicited by Shh may provide a rationale to design innovative therapeutic regimens for various neurodegenerative diseases.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Emerging Roles of Sonic Hedgehog in Adult Neurological Diseases: Neurogenesis and Beyond

Chen

Yang

Hwang

et al. 2018

IJMS

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“…have tested whether epidural application of the biologically active N-terminal fragment of Shh (Shh-N) may reduce the extent of ischemic brain injury in rats exposed to a 60-min episode of middle cerebral artery occlusion. Shh-N was applied topically, by placing a fibrin glue over the peri-infarct cortex [46]. They found that such treatment substantially reduced infarct volumes after 7 days of reperfusion.…”

Section: Hedgehog In the Ischemic Brainmentioning

confidence: 99%

The Hedgehog Signaling Pathway in the Ischemic Heart, Brain, and Skeletal Muscle

Giarretta¹,

Gaetani²,

Tondi³

et al. 2018

Preprint

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Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in ischemic condition is also presented.

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“…In the pathological condition such as stroke, trauma and infection, or stimulation of other methods such as drugs, cells and rehabilitation, the Shh signaling could be activated. The activated Shh signaling can enhance viability, proliferation or differentiation of cells or stem cells, reduce damage and promote functional recovery via anti-apoptosis, anti-oxidation, anti-inflammation, and so on [29][30][31][32]. Moreover, more studies have shown that resveratrol can activate the Shh signaling [19,21,22,32].…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Activated Sonic Hedgehog Signaling to Enhance Viability of NIH3T3 Cells in Vitro via Regulation of Sirt1

Guo¹,

Liao²,

Liu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Injuries of the brain and spinal cord result in the formation of glial (reactive gliosis) and fibrotic (formed by fibroblasts) scars. Recent studies have shown that the fibrotic scar was much more important for hindering regeneration after brain or spinal cord injury than the astrocytic scar. However, it has been given much less attention for effects and mechanism of fibroblasts during formation of the fibrotic scar. Resveratrol may be a potential anti-scarring agent in burn-related scarring and keloid fibroblasts. However, it is unclear whether and how resveratrol affects formation of the fibrotic scar after brain or spinal cord injury. Earlier studies have shown that the activated Shh signaling has anti-apoptosis, anti-oxidation, anti-inflammation properties. Moreover, resveratrol can activate the Shh signaling. However, it is unclear how resveratrol activates the Shh signaling. Resveratrol is a activator of Sirt1. It is unknown whether resveratrol activates the Shh signaling via Sirt1. Methods: NIH3T3 cells, a fibroblast cell line, were used as model cells and treated with drugs. Cell viability was assessed by Cell Counting Kit 8. The expressions and activity of Shh signaling pathway proteins were evaluated by immunocytochemistry and Western blotting. Transcriptional activity of Gli-1 was detected with Dual-Luciferase Reporter Gene Assay Kit. Results: Resveratrol, Sirt1 agonist STR1720 and recombinant mouse Shh protein, an activator of hedgehog signaling, enhanced the viability of NIH3T3 cells, promoted Smo to translocated to the primary cilia and Gli-1 entered into the nuclei from cytoplasm, and upregulated expressions of Shh, Ptc-1, Smo, and Gli-1 proteins, which can be reversed by Smo antagonist cyclopamine and Sirt1 antagonist Sirtinol. Additionally, resveratrol increased transcriptional activity of Gli-1. Conclusion: We indicate in the first time that it may be mediated by Sirt1 for resveratrol activating the Shh signaling to enhance viability of NIH3T3 cells, and Sirt1 may be a regulator for upstream of the Shh signaling pathway.This study provides a basis for further investigating effects and mechanism of resveratrol during the formation of fibrous scar after brain or spinal cord injury.

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Anti-oxidative, anti-apoptotic, and pro-angiogenic effects mediate functional improvement by sonic hedgehog against focal cerebral ischemia in rats

Cited by 56 publications

References 40 publications

Emerging Roles of Sonic Hedgehog in Adult Neurological Diseases: Neurogenesis and Beyond

Emerging Roles of Sonic Hedgehog in Adult Neurological Diseases: Neurogenesis and Beyond

The Hedgehog Signaling Pathway in the Ischemic Heart, Brain, and Skeletal Muscle

Resveratrol Activated Sonic Hedgehog Signaling to Enhance Viability of NIH3T3 Cells in Vitro via Regulation of Sirt1

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