CELL BIOLOGY INTERNATIONAL
·
2018
·Vol. 42
·期 11
·1584-1593
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IF 1.936
Bo Yu,Yanan Zhao,Hongli Zhang,Di Xie,Wei Nie,Kaiyao Shi
MicroRNA-143-3p (miR-143-3p) is involved in the initiation of inflammatory response and the progression of cardiovascular diseases. Myocardial hypertrophy is a common symptom in numerous cardiovascular diseases. In the current study, we attempted to demonstrate the role of miR-143-3p in the development of myocardial hypertrophy by focusing on its association with inflammation. Myocardial hypertrophy was induced by transverse aortic constriction (TAC) method in vivo and by H 2 O 2 administration in vitro. The expression status of miR-143-3p and downstream effectors were detected in animal heart tissues and H9c2 cells. Furthermore, the effect of miR-143-3p inhibition on H 2 O 2 -induced changes in ERK5/PPARδ/NF-κB axis was assessed. TAC induced oxidative stress and inflammation in rat heart tissues, which was associated with the increased expressions of miR-143-3p and p-ERK5. However, the up-regulated expression of miR-143-3p had no effect on the expression of ERK5, which was a direct target of miR-143-3p. The results of in vitro assays showed that H 2 O 2 administration increased the levels of miR-143-3p and p-EKR5 and induced the activation of NF-κB pathway. After the inhibition of miR-143-3p, the activation of EKR5 and NF-κB pathway was suppressed, whereas the expression of PPARδ was up-regulated. The current study demonstrated that miR-143-3p is crucial to the initiation of inflammatory response induced by myocardial hypertrophy. The activation of ERK5 following miR-143-3p up-regulation appears to be a complementary response to induce the subsequent anti-inflammatory signaling transduction, which needed further exploration.
研究领域:
心血管疾病
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分子生物学
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炎症
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DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 5
·1958-1972
·
IF 5.396
Zhaohui Xue,Xin Gao,Wancong Yu,Qian Zhang,Weichen Song,Shihao Li,Xu Zheng,Xiaohong Kou
Urban particulate matter (UPM), an air pollutant-absorbing toxic substance, can access alveoli, leading to pulmonary diseases. Studies have shown that the water-soluble components of UPM (WS-UPM), containing main toxic substances, can induce oxidative damage in lung cells. In this study, the UPM particle size and composition were detected via instrumental analysis. The isoflavones (biochanin A (BCA), formononetin and daidzein) from chickpeas possess biological antioxidant properties. The present study aimed to investigate the mechanism of the oxidative damage induced by WS-UPM, and the protective role of isoflavones in human alveolar basal epithelial cells. The antioxidant activity of BCA, formononetin and daidzein was investigated through the total reduction capacity, diphenylpicrylhydrazine radical (DPPH), superoxide radical, and hydroxyl radical scavenging capacity detection. We also established cell models in vitro to further explore the BCA-protective mechanism. BCA presented a significant protection, and increased the levels of antioxidant makers including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). The effects were also reflected as the reduction of malondialdehyde (MDA) and nitric oxide (NO). Moreover, results obtained from RT-PCR and western blot techniques revealed that MEK5/ERK5 played an indispensable role in regulating the antioxidant effect of BCA, alleviating WS-UPM-induced lung injury. Furthermore, BCA mitigated WS-UPM-exposed damage through upregulating the Nrf2 signaling pathway to enhance the antioxidase expression downstream of Nrf2. In summary, our findings indicated that the WS-UPM-induced pulmonary disease was involved in oxidative stress and the MEK5/ERK5-Nrf2 signaling pathway, and BCA regulated the WS-UPM-induced lung damage via upregulation of the MEK5/ERK5-Nrf2 pathway.
研究领域:
环境科学
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毒理学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2018
·Vol. 176
·期 3
·416-435
·
IF 6.81
Jingyan Li,Junying Huang,Jing Lu,Zhen Guo,Zhuoming Li,Hui Gao,Panxia Wang,Wenwei Luo,Sidong Cai,Yuehuai Hu,Kaiteng Guo,Luping Wang,Zhenzhen Li,Minghui Wang,Xiaolei Zhang,Peiqing Liu
Background and Purpose Activation of PKC-ζ is closely linked to the pathogenesis of cardiac hypertrophy. PKC-ζ can be activated by certain lipid metabolites such as phosphatidylinositol (3,4,5)-trisphosphate and ceramide. However, its endogenous negative regulators are not well defined. Here, the role of the sirtuin1-PKC-ζ signalling axis and the underlying molecular mechanisms were investigated in cardiac hypertrophy. Experimental Approach Cellular hypertrophy in cultures of cardiac myocytes, from neonatal Sprague-Dawley rats, was monitored by measuring cell surface area and the mRNA levels of hypertrophic biomarkers. Interaction between sirtuin1 and PKC-ζ was investigated by co-immunoprecipitation and confocal immunofluorescence microscopy. Sirtuin1 activation was enhanced by resveratrol treatment or Ad-sirtuin1 transfection. A model of cardiac hypertrophy in Sprague-Dawley rats was established by abdominal aortic constriction surgery or induced by isoprenaline in vivo . Key Results Overexpression of PKC-ζ led to cardiac hypertrophy and increased activity of NF-κB, ERK1/2 and ERK5, which was ameliorated by sirtuin1 overexpression. Enhancement of sirtuin1 activity suppressed acetylation of PKC-ζ, hindered its binding to phosphoinositide-dependent kinase 1 and inhibited PKC-ζ phosphorylation in cardiac hypertrophy. Consequently, the downstream pathways of PKC-ζ' were suppressed in cardiac hypertrophy. This regulation loop suggests a new role for sirtuin1 in mediation of cardiac hypertrophy. Conclusions and Implications Sirtuin1 is an endogenous negative regulator for PKC-ζ and mediates its activity via regulating the acetylation and phosphorylation in the pathogenesis of cardiac hypertrophy. Targeting the sirtuin1-PKC-ζ signalling axis may suggest a novel therapeutic approach against cardiac hypertrophy.
研究领域:
心脏病学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
REDOX REPORT
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2024
·
IF 5.2
Hanan M. Hassan,Ahmed M. Hamdan,Abdullah Alattar,Reem Alshaman,Omar Bahattab,Mohammed M. H. Al-Gayyar
Emodin is a naturally occurring anthraquinone derivative with a wide range of pharmacological activities, including neuroprotective and anti-inflammatory activities. We aim to assess the anticancer activity of emodin against hepatocellular carcinoma (HCC) in rat models using the proliferation, invasion, and angiogenesis biomarkers. After induction of HCC, assessment of the liver impairment and the histopathology of liver sections were investigated. Hepatic expression of both mRNA and protein of the oxidative stress biomarkers, HO-1, Nrf2; the mitogenic activation biomarkers, ERK5, PKCδ; the tissue destruction biomarker, ADAMTS4; the tissue homeostasis biomarker, aggregan; the cellular fibrinolytic biomarker, MMP3; and of the cellular angiogenesis biomarker, VEGF were measured. Emodin increased the survival percentage and reduced the number of hepatic nodules compared to the HCC group. Besides, emodin reduced the elevated expression of both mRNA and proteins of all PKC, ERK5, ADAMTS4, MMP3, and VEGF compared with the HCC group. On the other hand, emodin increased the expression of mRNA and proteins of Nrf2, HO-1, and aggrecan compared with the HCC group. Therefore, emodin is a promising anticancer agent against HCC preventing the cancer prognosis and infiltration. It works through many mechanisms of action, such as blocking oxidative stress, proliferation, invasion, and angiogenesis.
研究领域:
药理学
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肿瘤学
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分子生物学
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病理学
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DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Peidong You,Anning Yang,Yue Sun,Hongwen Zhang,Yaling Zeng,Yinju Hao,Jiantuan Xiong,Shengchao Ma,Huiping Zhang,Bin Liu,Yideng Jiang
Atherosclerosis is chronic inflammatory disease tightly related with defective efferocytosis of apoptotic cells (ACs) in the plaques. The strategy of efferocytosis reactivation using Atorvastatin (AT) and Metformin (Met) has attracted increasing attention for atherosclerosis treatment. Although these drug-based therapies could stimulate the phagocytic clearance of ACs, the rapid drug clearance and poor bioavailability limited their efficacy. In this study, by co-loading AT and Met into poly(lactic-co-glycolic) acid nanoparticles (PLGA NPs), we developed a biomimetic nanocomplexes for targeted atherosclerosis treatment. Macrophages membrane-coated nanocomplexes efficiently avoided the clearance of NPs from immune system and achieved targeting ability to the atherosclerotic plaques. Moreover, modified hyaluronic acid (HA) delivered NPs into the dysfunctional efferocytic cells of plaques, and achieved the plaques-macrophages-targeted therapy. In vitro results indicated that the biomimetic nanocomplexes reactivated efferocytosis by facilitating macrophages polarization from M1 to M2 phenotype through enhancing ERK5/MerTK pathway and inhibiting cellular senescence through inhibiting p53-p16/pRB pathway. In vivo study indicated that this biomimetic nanocomplexes accumulated in the atherosclerotic plaques, resulting in reduction of necrotic core area and protection against plaque rupture by reactivating efferocytosis. These findings indicated that reactivation of efferocytosis by AT and Met co-delivered nanocomplexes provided a novel promising strategy for targeted atherosclerosis treatment.
研究领域:
心血管疾病
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纳米技术
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药学
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生物医学工程
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DOI
高影响因子
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