Last update 19 Sep 2024

SLC39A12

Last update 19 Sep 2024

Basic Info

Synonyms

FLJ30499, LIV-1 subfamily of ZIP zinc transporter 8, LZT-Hs8

+ [8]

Introduction

Uniporter that promotes Zn(2+) import from the extracellular space to the cytoplasm across the cell membrane. The transport activity is temperature dependent. May play a role in neurulation and neurite extension. May play a key role in maintaining intracellular zinc content at levels that reduce the inhibitory effects of rises in oxidative stress on spermatogonia and spermatozoa viability during spermatogenesis.

Drugs associated with SLC39A12

APL-9796

Target

SLC39A12

Mechanism

SLC39A12 blockers

Active Org.

Apollo Therapeutics LLPStartup

Originator Org.

Apollo Therapeutics LLPStartup

Active Indication

Pulmonary Arterial Hypertension

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with SLC39A12

100 Translational Medicine associated with SLC39A12

0 Patents (Medical) associated with SLC39A12

Literatures (Medical) associated with SLC39A12

01 Dec 2024·Journal of Trace Elements in Medicine and Biology

Distinctive expression and cellular localisation of zinc homeostasis-related proteins in breast and prostate cancer cells

Article

Author: Nesarajah, Abinaya N ; Zaman, Mohammad S ; Barman, Shital K ; Wu, Ming J ; Malladi, Chandra S ; Mahns, David A

BACKGROUNDZinc transport proteins (ZIP and ZnT), metallothioneins (MT) and protein kinase CK2 are involved in dysregulation of zinc homeostasis in breast and prostate cancer cells. Following up our previous research, we targeted ZIP12, ZnT1, MT2A and CK2 in this study by investigating their expression levels and protein localisation.METHODSQuantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence confocal microscopy were employed to quantify the expression of ZIP12, ZnT1, MT2A and CK2 subunits in a panel of breast and prostate cell lines without or with extracellular zinc exposure. The cellular localisations of these target proteins were also examined by immunofluorescence confocal microscopy.RESULTSIn response to the extracellular zinc exposure, the gene expression was elevated for SLC39A12 (ZIP12), SLC30A1 (ZnT1) and MT2A (MT2A) in normal prostate epithelial cells (RWPE-1) in contrast to their cancerous counterparts (PC3 and DU145), whilst the gene expression was higher for SLC39A12 (ZIP12) and SLC30A1 (ZnT1) in both normal (MCF10A) and basal breast cancer cells (MDA-MB-231) compared to luminal breast cancer cells (MCF-7). At the protein level, the expression for both ZIP12 and ZnT1 was trending lower in the time course for the breast cancer cells whilst their expression was remained constant in the normal breast epithelial cells. The expression of ZIP12 in prostate cancer cells was higher than the normal prostate cells. The protein expression for CK2 α/αꞌ and CK2β was markedly higher in prostate cancer cells than the normal prostate cells. Upon extracellular zinc exposure, ZIP12 was, for the first time, conspicuously localised in the plasma membrane of breast cancer cells but not in normal breast epithelial cells and prostate cells. ZnT1 is only localised in the plasma membrane of breast cancer cells. MT2A is distinctively seen close to the plasma membrane in breast cancer cells. CK2 is also for the first time shown to be localised in proximity to the plasma membrane of breast cancer cells.CONCLUSIONThe findings, particularly the localisation of ZIP12 and CK2, are novel and significant for our understanding of zinc homeostasis in breast and prostate cancer cells.

01 Oct 2024·Biological Trace Element Research

Upregulation of Intracellular Zinc Ion Level after Differentiation of the Neural Stem/Progenitor Cells In Vitro with the Changes in Gene Expression of Zinc Transporters

Article

Author: Goji, Akari ; Hara, Masayuki ; Mori, Hideki

We measured the intracellular zinc ion concentration of murine fetal neural stem/progenitor cells (NSPCs) and that in the differentiated cells. The NSPCs cultured with 1.5 μM Zn²⁺ proliferated slightly faster than that in the zinc-deficient medium and the intracellular zinc concentration of the NSPCs and that of their differentiated cells (DCs) cultured with 1.5 μM Zn²⁺ was 1.34-fold and 2.00-fold higher than those in the zinc-deficient medium, respectively. The zinc transporter genes upregulated over the 3.5-fold change were Zip1, Zip4, Zip12, Zip13, ZnT1, ZnT8, and ZnT10 whereas the only downregulated one was Zip8 during the differentiation of NSPCs to DCs. The cell morphologies of both NSPCs and DCs in the low oxygen culture condition consisting of 2%O₂ and 5%CO₂, the high carbon dioxide condition consisting of 21%O₂ and 10%CO₂, and the normal condition consisting of 21%O₂ and 5%CO₂ were essentially the same each other. The expression of Zip4, Zip8, Zip12, and Zip14 was not drastically changed depending on the O₂ and CO₂ concentrations.

01 Sep 2024·Journal of Psychiatric Research

Changes in levels of the zinc transporter SLC39A12 in Brodmann's area 44: Effects of sex, suicide, CNS pH and schizophrenia

Article

Author: Dean, Brian ; Hopper, Shaun ; Scarr, Elizabeth

Disturbed CNS zinc homeostasis is suggested as part of the pathophysiology of schizophrenia. Our data, from multiple studies, suggests levels of cortical RNA for the solute carrier family 39 member 12 (SLC39A12), a putative zinc transporter, is higher in people with schizophrenia and is more perturbed in a sub-group of people with the disorder that can be separated because they have very low levels of muscarinic M1 receptors (MRDS). In this study qPCR was used to measure levels of two RNA splice variants of SLC39A12 (a and b) in Brodmann's area (BA) 44 from new cohorts of controls and people with schizophrenia. For the first time, in our study cohort as a whole, we report levels of both splice variants of SLC39A12 are lower in females compared to males and there are correlations between levels of SLC39A12 a and b and CNS pH. Levels of both splice variants were also lower in people with schizophrenia who were suicide completers compared to those who were not. Accounting for these factors, we showed levels of SLC39A12 a and b were higher in BA 44 in schizophrenia compared to controls. In further analyses, with and without our previous data on SLC39A12 a and b, we confirmed changes in levels of SLC39A12 RNAs were more profound in MRDS. In conclusion, our study argues there are higher levels of SLC39A12 a and b in BA 44 in schizophrenia which could be contributing to the breakdown in CNS zinc homeostasis suggested as part of the pathophysiology of schizophrenia, particularly in those with MRDS.

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SLC39A12

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