Neuroprotective effect of tetramethylpyrazine against all-trans-retinal toxicity in the differentiated Y-79 cells via upregulation of IRBP expression

Wang, Ke; Zhu, Xue; Zhang, Kai; Zhou, Fanfan; Zhu, Ling

doi:10.1016/j.yexcr.2017.08.002

Cited by 11 publications

(5 citation statements)

References 41 publications

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“…Previously, TMP has been reported to exhibit neuropro-tective effects against retinal diseases in a number of in vitro and in vivo studies (43-45). Wang et al (46) found that the protective effects of TMP against all-trans-retinal toxicity in differentiated Y-79 cells, an in vitro model of photoreceptors, were mediated via upregulation of interphotoreceptor retinoid-binding protein expression. Yu et al (47) revealed that TMP attenuated transforming growth factor-β-induced pathological changes in the trabecular meshwork through the C-X-C chemokine receptor type 4 pathway, indicating that TMP is a potential therapeutic method for treating primary open-angle glaucoma; the roles of TMP in glaucoma require further investigation.…”

Section: Discussionmentioning

confidence: 99%

Tetramethylpyrazine protects retinal ganglion cells against H2O2‑induced damage via the�microRNA‑182/mitochondrial pathway

Wang

Ren

et al. 2019

Int J Mol Med

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Glaucoma is the leading cause of irreversible blindness worldwide; the apoptosis of the retinal ganglion cells (RGCs) is a hallmark of glaucoma. Tetramethylpyrazine (TMP) is the main active component of Ligusticum wallichii Franchat , and has been demonstrated to improve a variety of injuries through its antioxidative and antiapoptotic properties. However, these effects of TMP on glaucoma have not been studied. The present study aimed to investigate the potential role of TMP in glaucoma and to elucidate its possible mechanisms responsible for these effects. An in vitro model was generated, in which primary RGCs (PRGCs) were treated with H 2 O 2 . Our study revealed that TMP protected against H 2 O 2- induced injury to PRGCs, as evidenced by enhanced cell viability, reduced caspase 3 activity and decreased cell apoptosis. We also reported that TMP treatment inhibited reactive oxygen species (ROS) production and malondialdehyde levels, but upregulated the antioxidative enzyme superoxide dismutase. In particular, TMP significantly increased the expression of microRNA-182-5p (miR-182) in H 2 O 2 -treated PRGCs, which was selected as the target miRNA for further research. In addition, our findings suggested that the protective effects of TMP on H 2 O 2 -induced injury were attenuated by knockdown of miR-182. The results of a luciferase reporter assay demonstrated that Bcl-2 interacting protein 3 (BNIP3), an effector of mitochondria-mediated apoptosis, was a direct target of miR-182. In addition, TMP treatment significantly decreased the expression of BNIP3, Bax, cleaved-caspase-3 and cleaved-poly(ADP-ribose)polymerase, but increased that of Bcl-2. Also, TMP treatment decreased the release of cytochrome c from mitochondria and improved mitochondrial membrane potential in H 2 O 2 -treated RGCs. Of note, the inhibitory effects of TMP on the mitochondrial apoptotic pathway were suggested to be reversed by knockdown of miR-182. Collectively, our findings provide novel evidence that TMP protects PRGCs against H 2 O 2 -induced damage through suppressing apoptosis and oxidative stress via the miR-182/mitochondrial apoptotic pathway.

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Section: Discussionmentioning

confidence: 99%

Tetramethylpyrazine protects retinal ganglion cells against H2O2‑induced damage via the�microRNA‑182/mitochondrial pathway

Wang

Ren

et al. 2019

Int J Mol Med

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“…Tetramethylpyrazine, which has been widely used in treating cardiovascular diseases for over 40 years, was found to attenuate all-trans-retinal -induced cytotoxicity in the differentiated Y79 cells via suppressing oxidative and nitrosative stress, apoptosis and leukostasis (Zhao et al, 2016). A further study found that the neuroprotective effect of tetramethylpyrazine against all-trans-retinal toxicity is also mediated through upregulating IRBP expression (Wang et al, 2017). Therefore, some small molecules have the potential to protect photoreceptors from stress by increasing IRBP expression.…”

Section: Small Moleculesmentioning

confidence: 95%

Interphotoreceptor Retinoid-Binding Protein (IRBP) in Retinal Health and Disease

Zeng

Zhang

Madigan

et al. 2020

Front. Cell. Neurosci.

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Interphotoreceptor retinoid-binding protein (IRBP), also known as retinol binding protein 3 (RBP3), is a lipophilic glycoprotein specifically secreted by photoreceptors. Enriched in the interphotoreceptor matrix (IPM) and recycled by the retinal pigment epithelium (RPE), IRBP is essential for the vision of all vertebrates as it facilitates the transfer of retinoids in the visual cycle. It also helps to transport lipids between the RPE and photoreceptors. The thiol-dependent antioxidant activity of IRBP maintains the delicate redox balance in the normal retina. Thus, its dysfunction is suspected to play a role in many retinal diseases. We have reviewed here the latest research on IRBP in both retinal health and disease, including the function and regulation of IRBP under retinal stress in both animal models and the human retina. We have also explored the therapeutic potential of targeting IRBP in retinal diseases. Although some technical barriers remain, it is possible that manipulating the expression of IRBP in the retina will rescue or prevent photoreceptor degeneration in many retinal diseases.

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“…TMP has been reported to induce apoptosis in some cancer cells[ 14 - 17 ]. To determine whether TMP similarly induces colon cancer cell apoptosis, we performed Annexin-V/PI double staining and analyzed cell apoptosis.…”

Section: Resultsmentioning

confidence: 99%

Tetramethylpyrazine inhibits proliferation of colon cancer cells in vitro

Hou

et al. 2021

WJCC

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BACKGROUND Colon cancer is one of the most common malignancies worldwide, and chemotherapy is a widely used strategy in colon cancer clinical therapy. However, chemotherapy resistance is a major cause of disease recurrence and progression in colon cancer, and thus novel drugs for treatment are urgently needed. Tetramethylpyrazine (TMP), a component of the traditional Chinese medicine Chuanxiong Hort, has been proven to exhibit a beneficial effect in tumors. AIM To investigate the potential anticancer activity of TMP in colon cancer and its underlying mechanisms. METHODS Colon cancer cells were incubated with different concentrations of TMP. Cell viability was evaluated by crystal violet staining assay and cell counting kit-8 assay, and cell apoptosis and cell cycle were assessed by flow cytometry. RESULTS TMP significantly inhibited the proliferation of colon cancer cells in a dose- and time-dependent manner. In addition, flow cytometry revealed that TMP induced cell cycle arrest at the G0/G1 phase. TMP treatment caused early stage apoptosis in SW480 cells, whereas it caused late stage apoptosis in HCT116 cells. CONCLUSION Our studies demonstrated that TMP inhibits the proliferation of colon cancer cells in a dose- and time-dependent manner by inducing apoptosis and arresting the cell cycle at the G0/G1 phase. Our findings suggest that TMP might serve as a potential novel therapeutic drug in the treatment of human colon cancer.

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Neuroprotective effect of tetramethylpyrazine against all-trans-retinal toxicity in the differentiated Y-79 cells via upregulation of IRBP expression

Cited by 11 publications

References 41 publications

Tetramethylpyrazine protects retinal ganglion cells against H2O2‑induced damage via the�microRNA‑182/mitochondrial pathway

Tetramethylpyrazine protects retinal ganglion cells against H2O2‑induced damage via the�microRNA‑182/mitochondrial pathway

Interphotoreceptor Retinoid-Binding Protein (IRBP) in Retinal Health and Disease

Tetramethylpyrazine inhibits proliferation of colon cancer cells in vitro

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