Investigation of nickel sulfate‐induced cytotoxicity and underlying toxicological mechanisms in human umbilical vein endothelial cells through oxidative stress, inflammation, apoptosis, and MAPK signaling pathways

氧化应激 脐静脉 活性氧 细胞凋亡 MAPK/ERK通路 p38丝裂原活化蛋白激酶 超氧化物歧化酶 丙二醛 谷胱甘肽 化学 信号转导 活力测定 脂质过氧化 炎症 细胞生物学 生物化学 生物 分子生物学 免疫学 体外
作者
Yanli Liu,Xia Gong,Juan Wang,Yongxiang Wang,Yong Zhang,Tao Li,Juan Yan,Min Zhou,Benzhong Zhang
出处
期刊:Environmental Toxicology [Wiley]
卷期号:37 (8): 2058-2071 被引量:11
标识
DOI:10.1002/tox.23550
摘要

Growing evidence indicates that nickle and its compounds have adverse effects on the cardiovascular system. In this study, the cytotoxic insults caused by nickel sulfate (NiSO4 ) in human umbilical vein endothelial cells (HUVECs) were explored by examining cell viability, oxidative stress, inflammation, apoptosis, and MAPK signaling pathway activity. Cultured HUVECs were treated with varying concentrations of NiSO4 (0, 62.5, 250, and 1000 μM) for 24 h. Subsequently, markers of oxidative stress, inflammation, apoptosis, and MAPK signaling pathways were analyzed using biochemical assays, real-time quantitative polymerase chain reaction, and western blot. Rates of apoptosis were evaluated using flow cytometry. The results showed that NiSO4 exerted dose- and time-dependent inhibitory effects on cell growth. It induced oxidative stress and lipid peroxidation by increasing the generation of reactive oxygen species, the oxidized glutathione to reduced glutathione ratio (GSSG/GSH ratio), and malondialdehyde levels. Further, it inhibited superoxide dismutase activity in HUVECs. Flow cytometry analysis results revealed that NiSO4 (62.5-1000 μM) could induce apoptosis in HUVECs. The protein and gene expressions of cleaved Caspase 3 and Bax were elevated, and those of Bcl-2 and Bcl-XL were reduced after NiSO4 treatment. Additionally, NiSO4 triggered inflammation in HUVECs, increasing the protein and mRNA levels of IL-6 and TNF-α and reducing those of TGF-β. Furthermore, western blot findings revealed that NiSO4 could activate MAPK signaling pathways, upregulating p38, JNK, and ERK1/2 in HUVECs by increasing the levels of p-P38,p-JNK, and p-ERK1/2 in a dose-dependent manner. MAPK pathway inhibitors (10 μM SB203580 and 10 μM SP600125) could attenuate the NiSO4 -induced increase in apoptosis and inflammation in HUVECs. They could also attenuate the dysregulation of inflammatory factors and related proteins caused by high-dose NiSO4 exposure. Interestingly, while the MEK inhibitor U0126 (10 μM) enhanced NiSO4 -induced apoptosis in HUVECs, it reduced cell inflammation. Taken together, these experimental results suggest that NiSO4 can inhibit cell growth, induce oxidative stress, and trigger subsequent inflammatory responses and apoptosis in HUVECs. These effects may be mediated by the P38 and JNK MAPK stress response pathways.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
研友_VZG7GZ应助雪山飞龙采纳,获得10
2秒前
寻123发布了新的文献求助10
2秒前
4秒前
Kin_L应助火星上的幻雪采纳,获得10
4秒前
GY发布了新的文献求助10
5秒前
highrain发布了新的文献求助10
5秒前
5秒前
大大发布了新的文献求助10
6秒前
兰蕙完成签到,获得积分10
7秒前
科研通AI5应助zhang采纳,获得10
7秒前
寻123完成签到,获得积分10
8秒前
11秒前
科研通AI2S应助wangfeng007采纳,获得30
11秒前
11秒前
zxl发布了新的文献求助10
11秒前
ZJJ静完成签到,获得积分10
11秒前
13秒前
怕黑誉完成签到,获得积分10
13秒前
yy完成签到 ,获得积分10
16秒前
一川发布了新的文献求助10
16秒前
16秒前
16秒前
大大完成签到,获得积分10
18秒前
量子星尘发布了新的文献求助10
19秒前
科研小白完成签到 ,获得积分10
19秒前
20秒前
highrain完成签到,获得积分20
20秒前
20秒前
领导范儿应助666采纳,获得10
20秒前
bingbing发布了新的文献求助10
21秒前
22秒前
丘比特应助她很可疑啊采纳,获得10
23秒前
潘多拉完成签到,获得积分10
23秒前
情怀应助zxl采纳,获得10
24秒前
ZTX发布了新的文献求助30
24秒前
25秒前
25秒前
26秒前
哈皮关注了科研通微信公众号
27秒前
GY完成签到,获得积分10
27秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3969884
求助须知:如何正确求助?哪些是违规求助? 3514604
关于积分的说明 11174901
捐赠科研通 3249928
什么是DOI,文献DOI怎么找? 1795149
邀请新用户注册赠送积分活动 875599
科研通“疑难数据库(出版商)”最低求助积分说明 804891