摘要：
Formaldehyde (FA) has neurotoxic characteristics and causes neurodegenerative disease. Our previous study demonstrated the neuroprotective effects of hydrogen sulfide (H(2)S) on FA-induced neurotoxicity in HT22 cells. Emerging evidence have supported that ferroptosis is involved in FA-induced neurotoxicity. To understand the mechanism of the protection of H(2)S against FA-induced neurotoxicity, this study explored the regulatory effect of H(2)S on FA-induced ferroptosis and the underlying mechanisms. The researcher found that H(2)S (100, 200, and 400μM, 30min) reverses the ferroptosis induced by FA (100μM, 24h) in HT22 cells (a cell line of mouse hippocampal neurons), including decreases in free iron, reactive oxygen species (ROS), 4-hydroxy-2-trans-nominal (4-HNE), and malondialdehyde (MDA) contents, as well as an increase in glutathione (GSH) content. H(2)S (100, 200, and 400μM, 30min) also inhibited ferritinaphagy in FA-exposed HT22 cells, as evidenced by the downregulation of the ferritinophagy receptor nuclear receptor coactivator 4 (NCOA4) and microtubule-associated protein 1 light chain-3B (LC3B) as well as the upregulation of the main iron storage protein ferritin heavy chain 1 (FTH1) and p62. H(2)S (100, 200, and 400μM, 30min) also up-regulated the expression of growth differentiation factor-11 (GDF11) in FA-exposed HT22 cells. Furthermore, knockdown of GDF11 in HT22 cells cancelled the beneficial effects of H(2)S in FA-induced ferroptosis and ferritinaphagy. These data indicated that the protective mechanism underlying H(2)S-prevented neurotoxicity of FA is involved in alleviating FA-induced ferroptosis via inhibiting ferritinaphagy by upregulation of GDF11.
摘要：
Hyperglycemia, a key characteristic and risk factor for diabetes mellitus (DM), causes neuronal senescence. Hydrogen sulfide (H2S) is a novel neuroprotectant. The present work was to investigate the potential effect of H2S on hyperglycemia-induced neuronal senescence and the underlying mechanisms. We found that NaHS, a donor of H2S, inhibited high glucose (HG)-induced cellular senescence in HT22 cells (an immortalized mouse hippocampal cell line), as evidenced by a decrease in the number of senescence associated-β-galactosidase (SA-β-gal) positive cells, increase in the growth of cells, and down-regulations of senescence mark proteins, p16INK4a and p21CIP1. NaHS improved the autophagic flux, which is judged by a decrease in the amount of intracellular autophagosome as well as up-regulations of LC3II/I and P62 in HG-exposed HT22 cells. Furthermore, blocked autophagic flux by chloroquine (CQ) significantly abolished NaHS-exerted improvement in the autophagic flux and suppression in the cellular senescence of GH-exposed HT22 cells, which indicated that H2S antagonizes HG-induced neuronal senescence by promoting autophagic flux. We also found that NaHS up-regulated the expression of silent mating type information regulation 2 homolog 1 (SIRT1), an important anti-aging protein, in HG-exposed HT22 cells. Furthermore, inhibition of SIRT1 by sirtinol reversed the protection of H2S against HG-induced autophagic flux blockade and cellular senescence in HT22 cells. These data indicated that H2S protects HT22 cells against HG-induced neuronal senescence by improving autophagic flux via up-regulation of SIRT1, suggesting H2S as a potential treatment strategy for hyperglycemia-induced neuronal senescence and neurotoxicity.
摘要：
BACKGROUND/AIMS: Hypoxia can induce cell injury in cardiomyocytes and further lead to cardiovascular diseases. Genistein (Gen), the predominant isoflavone found in soy products, has shown protective effects on cardiovascular system. The aim of the present study was to investigate the cardioprotective effect of Gen against chemical hypoxia-induced injury. METHODS: Cobalt chloride (CoCl2) was administrated to trigger chemical hypoxia in H9c2 cardiomyocytes. Cell proliferation was detected by using MTT assay. The expression level of hypoxia-related proteins (hypoxia-inducible factor [HIF]-1alpha and Notch-1) and apoptosis-related proteins (B cell lymphoma [Bcl]-2, Bax, and caspase-3) were evaluated by Western blot analysis. RESULTS: In response to hypoxia, cell viability was reduced dramatically, whereas the expression of HIF-1alpha was upregulated. Hypoxia also induced cardiomyocytes apoptosis by reducing the ratio of Bcl-2/Bax and increasing expression of caspase-3. Interestingly, Gen attenuated CoCl2-induced cell death and suppressed HIF-1alpha expression, as well as upregulated the expression of Notch-1. Furthermore, Gen could antagonize CoCl2-induced apoptosis through upregulating Bcl-2/Bax ratio and inhibiting caspase-3 expression. CONCLUSIONS: Gen prevents chemical hypoxia-induced cell apoptosis through inhibition of the mitochondrial apoptotic pathway, exerting protective effects on H9c2 cardiomyocytes.
作者机构：
[Tang, Xiao-Qing; Huang, Hong-Lin; Wei, Le] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Wang, Chun-Yan; Tang, Xiao-Qing; Zou, Wei; Kan, Li-Yuan; Wei, Le; Zeng, Hai-Ying; Tang, Yi-Yun; Xie, Ming; Zhang, Ping] Univ South China, Med Coll, Dept Physiol, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Wang, Chun-Yan; Tang, Xiao-Qing; Zou, Wei; Kan, Li-Yuan; Wei, Le; Zeng, Hai-Ying; Tang, Yi-Yun; Xie, Ming; Zhang, Ping] Univ South China, Med Coll, Inst Neurosci, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Tang, Xiao-Qing; Kan, Li-Yuan; Xie, Ming] Univ South China, Affiliated Hosp 1, Dept Neurol, Hengyang 421001, Hunan, Peoples R China.;[Zou, Wei; Zeng, Hai-Ying; Zhang, Ping] Univ South China, Nanhua Affiliated Hosp, Dept Neurol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Huang, Hong-Lin; Tang, Xiao-Qing] H;Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy and Pharmacology, University of South China, 28 West Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.;Department of Physiology and Institute of Neuroscience, Medical College, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.;Department of Neurology, The First Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, People's Republic of China.
摘要：
Our previous works have shown that hydrogen sulfide (H2S) significantly attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and hippocampal endoplasmic reticulum (ER) stress. Brain-derived neurotrophic factor (BDNF) generates an antidepressant-like effect by its receptor tyrosine protein kinase B (TrkB). We have previously found that H2S upregulates the expressions of BDNF and p-TrkB in the hippocampus of CUMS-exposed rats. Therefore, the present work was to explore whether BDNF/TrkB pathway mediates the antidepressant-like role of H2S by blocking hippocampal ER stress. We found that treatment with K252a (an inhibitor of BDNF/TrkB pathway) significantly increased the immobility time in the forced swim test and tail suspension test and increased the latency to feed in the novelty-suppressed feeding test in the rats cotreated with sodium hydrosulfide (NaHS, a donor of H2S) and CUMS. Similarly, K252a reversed the protective effect of NaHS against CUMS-induced hippocampal ER stress, as evidenced by increases in the levels of ER stress-related proteins, glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein and cleaved caspase-12. Taken together, our results suggest that BDNF/TrkB pathway plays an important mediatory role in the antidepressant-like action of H2S in CUMS-exposed rats, which is by suppression of hippocampal ER stress. These data provide a novel mechanism underlying the protection of H2S against CUMS-induced depressive-like behaviors.
摘要：
Formaldehyde (FA), a common environmental contaminant, has toxic effects on the central nervous system (CNS). We have previously found that hydrogen sulphide (H2S), the third endogenous gaseous mediator, protects neuron against the toxicity of FA. However, the underlying mechanism is poor. Aldehyde-dehydrogenase-2 (ALDH2) plays a major role in detoxification of reactive aldehyde in a range of organs and cell types. Therefore, we speculated that H2S antagonizes FA-induced neurotoxicity by modulating ALDH2. In the present study, we found that the exposure of PC12 cells to FA causes increase in ALDH2 expression and activity. Daidzin, an inhibitor of ALDH2, significantly antagonizes FA-exerted cytotoxicity and oxidative stress including the accumulation of intracellular reactive oxygen species (ROS), 4-hydroxy-2-trans-nonenal (4-HNE), and malondialdehyde (MDA), in PC12 cells. We also showed that daidzin markedly attenuated FA-induced apoptosis in PC12 cells. Furthermore, we found that H2S reverses FA-elicited upregulation of ALDH2 in PC12 cells. Our results demonstrated the involvement of downregulation of ALDH2 in the protection of H2S against FA neurotoxicity.
通讯机构：
[He, Dongxiu] U;[He, Dongxiu] H;Univ South China, Inst Pharm & Pharmacol, Hengyang, Hunan, Peoples R China.;Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Hunan, Peoples R China.
摘要：
The aberrant expression of carbohydrates has been associated with the occurrence, growth, progression and metastasis of tumors. Tumor-associated carbohydrates may have great potential as tumor markers for the early diagnosis of hepatocellular carcinoma (HCC). Therefore, characterizing HCC-associated carbohydrate expression is of great importance to assist the early diagnosis of HCC. A fluorescence method for characterizing carbohydrates expressed on both normal human cells (LO2 cells and endothelial cells) and HCC cells (HepG2 cells) using functionalized quantum dots (QDs) has been proposed in this study. The QDs were successfully fabricated and covalently conjugated with Datura stramonium agglutinin (DSA) or Lens culinaris agglutinin (LCA) via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) coupling reaction. The formed functionalized QDs (lectin–QDs conjugates) were characterized using ultraviolet and fluorescence spectra, agarose gel electrophoresis, hemagglutination activity tests, lectin competitive-binding assay and carbohydrate inhibition assays. The functionalized QDs were found to retain stable fluorescence and carbohydrate recognition abilities. Significant differences of carbohydrates expressed between on the normal cells and the HepG2 cells were evaluated by fluorescence imaging and flow cytometric analysis. The experimental results illustrate that the functionalized QDs could be used as promising tools for monitoring in situ cell surface carbohydrate expression and evaluating the differences in the carbohydrates expressed on normal cells and tumor cells surfaces, which is very important for helping the early diagnosis of HCC.
作者机构：
[张秀芹; 黄红林; 汪煜华; 李冬花] Learning Key Laboratory for Pharmacoproteomics of Hunan Province, Institute of Pharmacy and Pharmacology, University of South China, Hengyang Hunan, 421001, China;Loudi Health School, Loudi Hunan, 417000, China;[刘玉玲] Learning Key Laboratory for Pharmacoproteomics of Hunan Province, Institute of Pharmacy and Pharmacology, University of South China, Hengyang Hunan, 421001, China, Loudi Health School, Loudi Hunan, 417000, China
期刊：
Lecture Notes in Electrical Engineering,2014年269 LNEE(4):3065-3069 ISSN：1876-1100
通讯作者：
Guo, Z.(guozifen@aliyun.com)
作者机构：
[Guo, Zifen; Huang, Honglin] Department of Pharmacy, University of South China, Hengyang 421001, China;[Feng, Yong] Student Affairs Department, University of South China, Hengyang 421001, China
会议名称：
5th International Symposium on IT in Medicine and Education, ITME 2013
作者机构：
[刘玉玲; 李金兰; 赵绿英; 高治平; 黄红林] Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang Hunan 421001, China
通讯机构：
[Zhao, L.-Y.] I;Institute of Pharmacy and Pharmacology, , Hengyang Hunan 421001, China
关键词：
染料木素;高脂血症;食饵性;大鼠;C-反应蛋白;对氧磷酶
摘要：
目的探讨染料木素(genistein,Gen)对大鼠食饵性高脂血症对氧磷酶(paraoxonase,PON1)活性及C-反应蛋白(C-reactive protein,CRP)的影响。方法健康SD大鼠40只,♀♂各半,随机分为以下5组:①普食组;②高脂血症模型组;③低剂量Gen(0.5 mg·kg~(-1)·d~(-1))组;④高剂量Gen(5 mg·kg~(-1)·d~(-1))组;⑤辛伐他汀(5 mg·kg~(-1)·d~(-1))阳性药物对照组;除普食组给以普通饲料喂养外,其他组均饲以高脂饲料喂养加敌百虫(10 mg·kg~(-1)·d~(-1))腹腔注射,建立食饵性高脂血症模型。各组大鼠连续喂养及同时用药8周,每2周测1次体重,根据体重调整用药量;定期取血检测胆碱酯酶(acetylcholine esterase,AChE)、血脂、丙二醛(ma-lonaldehyde,MDA)、PON1和CRP的含量,用苏木精/伊红(hematoxylin/eosin,HE)染色检测大鼠肝脏及主动脉弓病理形态变化。结果与模型组相比,高剂量Gen组与辛伐他汀组大鼠总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)及动脉粥样硬化指数(atherosclerotic index,AI)明显降低,高密度脂蛋白胆固醇(high density lipoprotein cholesterol/total cholesterol,HDL-C)与TC比值(HDL-C/TC)明显升高,血清MDA含量也明显降低,同时还能明显降低高脂饲料喂养加低剂量敌百虫腹腔注射致高脂血症大鼠血清CRP含量,提高PON1活性,改善大鼠肝与主动脉弓形态变化。结论Gen可以减轻高脂饲料喂养加敌百虫诱发的大鼠高脂血症;其作用机制可能与逆转血脂障碍,抑制过氧化脂质作用抗氧化,降低炎症因子CRP抗炎及通过PON1酶的调节有关。
