The human zinc transporter SLC39A8 (Zip8) is critical in zinc-mediated cytoprotection in lung epithelia

细胞保护 细胞内 运输机 下调和上调 肿瘤坏死因子α 化学 细胞生物学 细胞 基因敲除 信使核糖核酸 生物化学 生物 氧化应激 免疫学 细胞凋亡 基因 有机化学
作者
Beth Besecker,Shengying Bao,Barbara Bohacova,Audrey C. Papp,Wolfgang Sadée,Daren L. Knoell
出处
期刊:American Journal of Physiology-lung Cellular and Molecular Physiology [American Physiological Society]
卷期号:294 (6): L1127-L1136 被引量:143
标识
DOI:10.1152/ajplung.00057.2008
摘要

Zinc is an essential micronutrient and cytoprotectant involved in the host response to inflammatory stress. We tested whether zinc transporters, the critical regulators that maintain intracellular zinc concentrations, play a role in cell survival, particularly in lung epithelia, during inflammation. Initially, mRNA transcripts were quantitatively measured by RT-PCR for all known human zinc transporters, including 14 importers (SLC39A 1–14 ) and 10 exporters (SLC30A 1–10 ), in primary human lung epithelia obtained from multiple human donors and BEAS-2B cell cultures under baseline and TNF-α-stimulated conditions. While many zinc transporters were constitutively expressed, only SLC39A8 (Zip8) mRNA was strongly induced by TNF-α. Endogenous Zip8 protein was not routinely detected under baseline conditions. In sharp contrast, TNF-α induced the expression of a glycosylated protein that translocated to the plasma membrane and mitochondria. Increased Zip8 expression resulted in an increase in intracellular zinc content and coincided with cell survival in the presence of TNF-α. Inhibition of Zip8 expression using a short interfering RNA probe reduced cellular zinc content and impaired mitochondrial function in response to TNF-α, resulting in loss of cell viability. These data are the first to characterize human Zip8 and remarkably demonstrate that upregulation of Zip8 is sufficient to protect lung epithelia against TNF-α-induced cytotoxicity. We conclude that Zip8 is unique, relative to other Zip proteins, by functioning as an essential zinc importer at the onset of inflammation, thereby facilitating cytoprotection within the lung.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

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
1秒前
调皮的翠安完成签到,获得积分20
2秒前
FashionBoy应助gaobowang采纳,获得10
3秒前
5秒前
5秒前
6秒前
SHY完成签到,获得积分10
7秒前
李爱国应助小美酱采纳,获得10
7秒前
优雅沛文发布了新的文献求助10
8秒前
天天快乐应助星空_采纳,获得10
9秒前
10秒前
...00发布了新的文献求助10
13秒前
ZJHYNL应助南安采纳,获得10
13秒前
15秒前
小中完成签到,获得积分10
15秒前
16秒前
Yiy发布了新的文献求助10
17秒前
麻辣烫完成签到 ,获得积分10
18秒前
迫切完成签到,获得积分10
20秒前
ckl发布了新的文献求助10
21秒前
wanci应助wlei采纳,获得10
21秒前
端庄的访枫完成签到 ,获得积分10
25秒前
25秒前
gxmu6322发布了新的文献求助10
25秒前
28秒前
JiegeSCI完成签到,获得积分10
28秒前
30秒前
mtbean发布了新的文献求助10
31秒前
叶泠渊发布了新的文献求助10
33秒前
神说应助ppplll采纳,获得10
34秒前
无辜大侠发布了新的文献求助10
35秒前
默默的裘完成签到,获得积分10
35秒前
山椒发布了新的文献求助10
36秒前
烟花应助霓娜酱采纳,获得10
36秒前
36秒前
37秒前
37秒前
科研顺利完成签到,获得积分20
38秒前
万能图书馆应助山椒采纳,获得10
40秒前
yt完成签到,获得积分10
40秒前
高分求助中
中国国际图书贸易总公司40周年纪念文集 大事记1949-1987 2000
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
草地生态学 880
Threaded Harmony: A Sustainable Approach to Fashion 799
Basic Modern Theory of Linear Complex Analytic 𝑞-Difference Equations 510
Queer Politics in Times of New Authoritarianisms: Popular Culture in South Asia 500
Livre et militantisme : La Cité éditeur 1958-1967 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 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 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3058489
求助须知:如何正确求助?哪些是违规求助? 2714529
关于积分的说明 7441097
捐赠科研通 2359812
什么是DOI,文献DOI怎么找? 1250399
科研通“疑难数据库(出版商)”最低求助积分说明 607442
版权声明 596410