A novel role for zinc transporter 8 in the facilitation of zinc accumulation and regulation of testosterone synthesis in Leydig cells of human and mouse testicles

Zhang, Xiuli; Guan, Tingwen; Yang, Boxuan; Chen, Zhihong; Wang, Zhan-You; Gu, Harvest F.

doi:10.1016/j.metabol.2018.09.002

Cited by 31 publications

(21 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This gene, however, is also expressed in other tissues, while kidney is the second rich expressed organ (please see https://www.genecards.org/Search/ Keyword?queryString=Znt8). Furthermore, we have recently found that ZnT8 is expressed in Leydig cells, transports zinc into Leydig cell mitochondria with gonadotropin stimulation 15 . A global loss of ZnT8 gene in mice rather than β-cell-specific knockdown of ZnT8, leads to glucose intolerance, insulin resistance and worsen obesity in those high-fat diet feeding 30 .…”

Section: Discussionmentioning

confidence: 99%

“…Western blot analysis was performed as previously described 15,32 . Kidney tissues were homogenized in cold radio-immunoprecipitation assay lysis buffer, incubated on ice for 1 h, centrifuged at 12,000 × g for 20 min at 4°C and then the supernatants were transferred to a clean tube.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Zinc transporter 8 (ZnT8 also known as SLC30A8) is localized in insulin secretory granules in the islets of Langerhans and facilitates the accumulation of zinc from the cytoplasm into intracellular vesicles in pancreatic beta-cells 13,14 . Recently, we have reported that ZnT8 also transports zinc into Leydig cell mitochondria with gonadotropin stimulation and plays a role in testosterone production via the PKA signaling pathway 15 . ZnT8 has genetic, epigenetic and biological effects in the pathogenesis of diabetes 16 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of ZnT8 on epithelial-to-mesenchymal transition and tubulointerstitial fibrosis in diabetic kidney disease

Zhang¹,

Guan²,

Yang³

et al. 2020

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

Zinc transporter 8 (ZnT8) transports zinc ions for crystallization and storage of insulin in pancreatic beta-cells and ZnT8 dysfunction is involved in pathogenesis of diabetes. The current study aimed to investigate whether ZnT8 has effects in pathophysiology of diabetic kidney disease (DKD) by using animal models for diabetes, including STZ-induced diabetic, db/db, ZnT8-KO, ZnT8-KO-STZ and ZnT8-KO-db/db mice. Results demonstrated that urine albumin to creatinine ratio and epithelial-to-mesenchymal transition (EMT) were increased in kidneys of ZnT8-KO-STZ and ZnT8-KO-db/db mice compared with C57BL/6 J and ZnT8-KO mice, while serum TGF-β1, IL-6, and TNF-α levels were elevated in parallel. In kidneys of mice intercrossed between ZnT8-KO and STZ-induced diabetic or db/db mice, these three inflammatory factors, ACR and EMT were also found to be increased compared with C57BL/6J, db/db and ZnT8-KO mice. Furthermore, ZnT8 up-regulation by hZnT8-EGFP reduced the levels of high glucose (HG)-induced EMT and inflammatory factors in normal rat kidney tubular epithelial cell (NRK-52E cells). Expression of phosphorylated Smad2/Smad3 was up-regulated after HG stimulation and further enhanced by ZnT8 siRNA but down-regulated after hZnT8-EGFP gene transfection. The current study thus provides the first evidence that ZnT8 protects against EMT-tubulointerstitial fibrosis though the restrain of TGF-β1/Smads signaling activation in DKD.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Western Blot Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of ZnT8 on epithelial-to-mesenchymal transition and tubulointerstitial fibrosis in diabetic kidney disease

Zhang¹,

Guan²,

Yang³

et al. 2020

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

show abstract

“…Since ZnT8 associates with secretory vesicles in other cell types [6,23,24], we further investigated its intracellular localization in thyrocites by double staining cells with anti-ZnT8 antibodies and with the zinc specific fluorescent probe Fluozin-3.…”

Section: Resultsmentioning

confidence: 99%

“…Zn ions are known to accumulate in intracellular vesicles, which are especially abundant in endocrine cells, where they were shown to play a role in secretion in some cell types [5]. Zn involvement in insulin secretion has been extensively studied in pancreatic β-cells, but a broader role for this metal in endocrine tissues was proposed on the basis of the expression profile of vesicular Zn transporters associated with the secretory pathway [6,22,24]. The ZnT8 transporter, in particular, is necessary for insulin secretion in pancreatic β-cells, and we and others subsequently demonstrated its abundant expression in follicular cells of the thyroid gland, which actively secrete thyroid hormones, suggesting a potential role for Zn in this process [6,10,24,25].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Zn Depletion/Repletion in the Hormone-Secreting Thyroid Follicular Cell Line FRTL-5

Guantario¹,

Capolupo

Monti

et al. 2018

Nutrients

View full text Add to dashboard Cite

Zinc deficiency predisposes to a wide spectrum of chronic diseases. The human Zn proteome was predicted to represent about 10% of the total human proteome, reflecting the broad array of metabolic functions in which this micronutrient is known to participate. In the thyroid, Zn was reported to regulate cellular homeostasis, with a yet elusive mechanism. The Fischer Rat Thyroid Cell Line FRTL-5 cell model, derived from a Fischer rat thyroid and displaying a follicular cell phenotype, was used to investigate a possible causal relationship between intracellular Zn levels and thyroid function. A proteomic approach was applied to compare proteins expressed in Zn deficiency, obtained by treating cells with the Zn-specific chelator N,N,N′,N′-tetrakis (2-pyridylmethyl) ethylene-diamine (TPEN), with Zn repleted cells. Quantitative proteomic analysis of whole cell protein extracts was performed using stable isotope dimethyl labelling coupled to nano-ultra performance liquid chromatography-mass spectrometry (UPLC-MS). TPEN treatment led to almost undetectable intracellular Zn, while decreasing thyroglobulin secretion. Subsequent addition of ZnSO4 fully reversed these phenotypes. Comparative proteomic analysis of Zn depleted/repleted cells identified 108 proteins modulated by either treatment. Biological process enrichment analysis identified functions involved in calcium release and the regulation of translation as the most strongly regulated processes in Zn depleted cells.

show abstract

Association of SNPs in zinc transporter genes on seminal plasma zinc levels in humans

Deng¹,

Han

Ma³

et al. 2022

Biometals

View full text Add to dashboard Cite

A novel role for zinc transporter 8 in the facilitation of zinc accumulation and regulation of testosterone synthesis in Leydig cells of human and mouse testicles

Cited by 31 publications

References 43 publications

Effects of ZnT8 on epithelial-to-mesenchymal transition and tubulointerstitial fibrosis in diabetic kidney disease

Effects of ZnT8 on epithelial-to-mesenchymal transition and tubulointerstitial fibrosis in diabetic kidney disease

Proteomic Analysis of Zn Depletion/Repletion in the Hormone-Secreting Thyroid Follicular Cell Line FRTL-5

Association of SNPs in zinc transporter genes on seminal plasma zinc levels in humans

Contact Info

Product

Resources

About