Hemopexin is required for adult neurogenesis in the subventricular zone/olfactory bulb pathway

Zhu, Yanling; Qiu, Yang; Chen, Mengjia; Zhang, Yi; Cao, Li; Zhi-da, SU; Yuan, Yihang; Huang, Aijun; Pu, Yinyan; He, Cheng

doi:10.1038/s41419-018-0328-0

Cited by 8 publications

(9 citation statements)

References 63 publications

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“…The olfactory bulb together with hippocampal dentate gyrus subventricular and the sub-granular zones, represent the three regions in the brain that undergo adult neurogenesis; the process that maintains continuous turnover of bulbar interneurons. Granular and periglomerular neurons of OB are well known to be differentiating and from cell precursors located in the subventricular zone and migrating to OB where it can respond to odor stimulations ( 42 – 44 ). In this study, Ki67 positive cells, which represent the newly proliferating nerve cells, was observed in the control MOB.…”

Section: Discussionmentioning

confidence: 99%

Ocimum basilicum (Basil) Modulates Apoptosis and Neurogenesis in Olfactory Pulp of Mice Exposed to Chronic Unpredictable Mild Stress

et al. 2020

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Background: Ocimum basilicum (O. basilicum) was described to have antidepressant and anxiolytic activities. Although the relationship between the main olfactory bulb (MOB) and depression was recently reported, the chronic stress-induced dysfunction of the MOB is not clearly described. Objectives: This study aimed to assess the efficacy of inhalation of O. basilicum essential oils in improving chronic unpredictable mild stress (CUMS)-induced changes in MOB of mice and understand the mechanism underlying such effect. Materials and Methods: Adult male mice (n=40) were assigned into four groups included the control, CUMS-exposed, CUMS + fluoxetine (FLU), CUMS + O. basilicum. Behavioral changes, serum corticosterone level, and gene expression of GFAP, Ki 67, and caspase-3 were assessed using real-time PCR (RT-PCR). Histopathological and immunochemical examination of the MOB was performed. Results: FLU and O. basilicum significantly down-regulated (p = 0.002, p<0.001) caspase-3 gene expression indicating reduced apoptosis and up-regulated (p = 0.002, p < 0.001) Ki67 gene expression indicating enhanced neurogenesis in MOB, respectively. FLU and O. basilicum-treated mice markedly improved MOB mitral cell layer distortion and shrinkage induced by CUMS. Conclusion: O. basilicum relieved both biochemically and histopathological chronic stress-induced changes in the main olfactory bulb possibly through up-regulation of gene expression of GFAP and Ki67 and down-regulation of caspase-3 in the MOB.

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Section: Discussionmentioning

confidence: 99%

Ocimum basilicum (Basil) Modulates Apoptosis and Neurogenesis in Olfactory Pulp of Mice Exposed to Chronic Unpredictable Mild Stress

et al. 2020

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“…Abnormalities develop in the SV2/olfactory bulb pathways of HPX-null mice that impair neuroblast migration in the subventricular zone as well as the rostral migratory stream. Exogenous HPX inhibited apoptosis and promoted the migration and differentiation of cultured neural stem cells [123].…”

Section: Hemopexin Protects the Blood-brain Barriermentioning

confidence: 97%

What Is Next in This “Age” of Heme-Driven Pathology and Protection by Hemopexin? An Update and Links with Iron

2019

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This review provides a synopsis of the published literature over the past two years on the heme-binding protein hemopexin (HPX), with some background information on the biochemistry of the HPX system. One focus is on the mechanisms of heme-driven pathology in the context of heme and iron homeostasis in human health and disease. The heme-binding protein hemopexin is a multi-functional protectant against hemoglobin (Hb)-derived heme toxicity as well as mitigating heme-mediated effects on immune cells, endothelial cells, and stem cells that collectively contribute to driving inflammation, perturbing vascular hemostasis and blood–brain barrier function. Heme toxicity, which may lead to iron toxicity, is recognized increasingly in a wide range of conditions involving hemolysis and immune system activation and, in this review, we highlight some newly identified actions of heme and hemopexin especially in situations where normal processes fail to maintain heme and iron homeostasis. Finally, we present preliminary data showing that the cytokine IL-6 cross talks with activation of the c-Jun N-terminal kinase pathway in response to heme-hemopexin in models of hepatocytes. This indicates another level of complexity in the cell responses to elevated heme via the HPX system when the immune system is activated and/or in the presence of inflammation.

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“…Besides heme-scavenging, other functions of hemopexin include iron homeostasis, antioxidant protection, anti-inflammatory effects, signaling to promote cell survival, and gene expression [42,43]. Recently, hemopexin was demonstrated to promote neural stem-cell migration and differentiation into neurons and oligodendrocytes in vitro [44]. In relation to cancer, hemopexin was reported to be upregulated in pleural effusions of lung-cancer patients and in plasma of pancreatic-cancer patients before resection [45,46], and the fucosylated form of hemopexin was reported as an accurate serum marker for hepatocellular carcinoma [47,48].…”

Section: Plos Onementioning

confidence: 99%

Stromal expression of hemopexin is associated with lymph-node metastasis in pancreatic ductal adenocarcinoma

et al. 2020

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Pancreatic ductal adenocarcinoma is one of the most aggressive types of cancer. Certain proteins in the tumor microenvironment have attracted considerable attention owing to their association with tumor invasion and metastasis. Here, we used proteomics to identify proteins associated with lymph-node metastasis, which is one of the prognostic factors. We selected lymph node metastasis-positive and-negative patients (n = 5 each) who underwent pancreatectomy between 2005 and 2015 and subjected to comprehensive proteomic profiling of tumor stroma. A total of 490 proteins were detected by mass spectrometry. Software analysis revealed that nine of these proteins were differentially expressed between the two patient groups. We focused on hemopexin and ferritin light chain based on immunohistochemistry results. We assessed the clinicopathological data of 163 patients and found that hemopexin expression was associated with UICC N2 (p = 0.0399), lymph node ratio (p = 0.0252), venous invasion (p = 0.0096), and lymphatic invasion (p = 0.0232). Notably, in vitro assays showed that hemopexin promotes invasion of the pancreatic cancer cells. Our findings suggest that hemopexin is a lymph node metastasis-associated protein that could potentially serve as a useful therapeutic target or biomarker of pancreatic ductal adenocarcinoma.

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Hemopexin is required for adult neurogenesis in the subventricular zone/olfactory bulb pathway

Cited by 8 publications

References 63 publications

Ocimum basilicum (Basil) Modulates Apoptosis and Neurogenesis in Olfactory Pulp of Mice Exposed to Chronic Unpredictable Mild Stress

Ocimum basilicum (Basil) Modulates Apoptosis and Neurogenesis in Olfactory Pulp of Mice Exposed to Chronic Unpredictable Mild Stress

What Is Next in This “Age” of Heme-Driven Pathology and Protection by Hemopexin? An Update and Links with Iron

Stromal expression of hemopexin is associated with lymph-node metastasis in pancreatic ductal adenocarcinoma

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