Disease relevance of SLC30A1

• ZnT-1 is induced by transient ischemia of the forebrain [1].
• Silencing of ZnT-1 expression enhances heavy metal influx and toxicity [2].
• Human prostate cancer tissues expressed significantly lower levels of ZnT-1 gene in comparison with hyperplastic tissues [3].

Psychiatry related information on SLC30A1

• Alterations in zinc transporter protein-1 (ZnT-1) in the brain of subjects with mild cognitive impairment, early, and late-stage Alzheimer's disease [4].

High impact information on SLC30A1

• The heavy metal-induced expression of another MTF1 target gene, zinc transporter 1 (ZnT-1), was also down-regulated by Cr6+ [5].
• We detected expression of two other members of the hZnT family, hZnT1 and hZnT3, in human breast epithelial cells [6].
• Furthermore, Cd(2+)-induced neuronal death increased by approximately twofold after transfection with ZnT-1 siRNA [2].
• An increased cation influx rate, through the LTCC, was also recorded for Zn(2+) and Cd(2+) in cells treated with the ZnT-1 siRNA [2].
• In addition, ZnT-1 siRNA transfection of the ovarian granulosa cell line, POGRS1, resulted in a twofold increase in Cd(2+) influx rate via the LTCC [2].

Chemical compound and disease context of SLC30A1

• ZnT-1 reduces intracellular zinc accumulation and confers resistance against cadmium toxicity by a mechanism which is still unresolved [2].
• Taken together, our results indicate that endogenously-expressed ZnT-1, by modulating LTCC, has a dual role: regulating calcium influx, and attenuating Cd(2+) and Zn(2+) permeation and toxicity in neurons and other cell types [2].

Biological context of SLC30A1

• Furthermore, ZnT-1 may play a role in cellular ion homeostasis and thereby confer protection against pathophysiological events linked to cellular Ca(2+) or Zn(2+) permeation and cell death [7].
• Differential regulation of zinc efflux transporters ZnT-1, ZnT-5 and ZnT-7 gene expression by zinc levels: a real-time RT-PCR study [8].
• Complementation of a yeast Zn transport-defective mutant with a T. caerulescens cDNA library resulted in the recovery of a cDNA, ZNT1, that encodes a Zn transporter [9].
• Moreover in HepG2 cells, immunochemical and fluorescence techniques showed the presence and the localisation of the zinc membrane exporter ZnT-1 as a further mechanism of defence/homeostasis against zinc toxicity [10].
• Downregulation of ZnT-1 mRNA and partial loss of loosely bound Zn were observed with 50muM Cd [11].

Anatomical context of SLC30A1

• In enterocytes of the small intestine and renal tubular cells, ZnT-1 is localized to the basolateral membrane, suggesting an orientation that is consistent with zinc absorption/retention [12].
• Immunolocalization places ZnT-1 at the basolateral membrane of intestinal enterocytes and epithelial cells of the distal renal tubules [1].
• In the whole pancreas of 3-day-old rats, ZnT-1 was the only zinc transporter mRNA detected and its level was moderate [13].
• To evaluate the potential applications of using both zinc transporter genes as biomarkers of zinc status, we measured the expression levels of ZIP1 and ZNT1 in the peripheral leukocytes collected from 2 different age groups of Korean women [14].
• In the human placental cell line JAR, however, expression at the mRNA level of a number of Zn transporters is not modified by Zn availability, whilst ZnT1 and hZTL1/ZnT5 proteins are reduced under Zn-supplemented conditions [15].

Associations of SLC30A1 with chemical compounds

• Zinc or cadmium treatment up-regulated MTs, MTF-1 and ZnT-1 gene expression levels in both cell lines [3].
• This specific probe was used to examine the effect of zinc-methionine (ZnMet) administration on the mRNA expression of ZnT1 and on small intestinal development and functionality [16].

Regulatory relationships of SLC30A1

• Zinc has been shown to modify specifically the metabolism of cGMP, the activities of protein kinase C and mitogen activated protein kinases, and the activity of transcription factor MTF-1 which controls the transcription of the genes for metallothionein and the zinc transporter ZnT-1 [17].

Other interactions of SLC30A1

• These findings suggest that factors such as ZnT1 and metallothioneins other than ZnT3 are associated with the low intracellular zinc content in AIDL cells [18].
• Different induction of metallothioneins and Hsp70 and presence of the membrane transporter ZnT-1 in HepG2 cells exposed to copper and zinc [10].

Analytical, diagnostic and therapeutic context of SLC30A1

• Western blot and dot-blot analysis showed statistically significant (p 0.05) elevations of ZnT-1 in AD AMY, HPG, and IPL and significantly depleted ZnT-1 in AD SMTG compared to age-matched control subjects [4].
• Likely candidates include two proteins identified by molecular cloning termed zinc transporter 1 and divalent cation transporter DCT1 [19].
• Sequence analysis of ZNT1 indicated it is a member of a recently discovered micronutrient transport gene family which includes the Arabidopsis Fe transporter, IRT1, and the ZIP Zn transporters [9].
• Using real-time quantitative PCR, we showed that both zinc (Zn) and cadmium (Cd) transiently upregulate ZnT-1 mRNA to comparable levels [11].

References