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Levels of Zinc Transporters mRNA Depending on Zinc Status and HIV-1 Tat Induced Inflammation in Muscle (Rhabdomyosarcoma) and Monocyte (THP-1) Cell Lines

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Abstract

Monocytes and muscles demonstrate functionally contrasting behavior under conditions of zinc deficiency with relation to zinc storage system (muscle retain zinc in contrast to monocytes). We aimed to understand the effects of zinc status and HIV-1 Tat mediated inflammation on expression of zinc transporters in these types of cells. Expression of zinc transporters [ZnTs, ZIPs, and metallothionein (MT)] was quantified by qRT-PCR in RD, THP-1 cells separately and in co-cultured THP-1–RD cells. ZnT1 protein expression levels were confirmed by Western blot. Significant increase of MT and ZnT1 mRNA in response to zinc supplementation and decrease during zinc deficiency indicates significance of the genes encoding transporters in maintaining zinc homeostasis in these tissues. In the RD cells ZIP10 exhibited inverse relation to zinc status whereas no correlation was found in the THP-1 cells. Tat-induced inflammation resulted in the significant elevation of MT, IL6, ZIP7, ZIP8, ZIP9 transcripts in the co-cultured RD cells, whereas THP-1 cells demonstrated increased IL-1β levels and reduced levels of ZIP7 and ZIP14. Zinc status and HIV-1Tat induced inflammation appear to influence differential expression of MT, ZnTs, and ZIPs in the muscle and monocyte cells.

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Abbreviations

DMEM:

Dulbecco’s modified eagle medium

FBS:

fetal bovine serum

gp120:

glycoprotein120

HIV:

Human Immunodeficiency Virus

IL:

interleukin

MT:

metallothionein

MTF:

metal transcription factor

MHC:

major histocompatibility complex

Tat:

trans-activator of transcription (Tat)

TNF:

tumour necrosis factor-α

RD:

rhabdomyosarcoma cells

TPEN:

N,N,N′,N′TetraKis (2-pyridylmethyl) ethylene diamine

ZIPs:

Zrt- and Irt-like protein

ZnTs:

zinc transporters

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Acknowledgements

We acknowledge CSIR-New Delhi, India, for financial assistance to Mr. Kiran Alluri for JRF and SRF (09/484/(0050)/2012-EMR-1). Authors gratefully acknowledge the support of Dr. B. Dinesh Kumar, Scientist G & Head-DTRC for extending the facility and chemicals/reagents from ICMR-Taskforce Project Ref. No. HIV/62/47/2016-ECD-II.

Funding

This research was financially supported by the Indian Council of Medical Research (intramural grants to KMN and grant to SG (5/9/1137/2014-NUT).

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Authors and Affiliations

  1. Molecular Biology Division, ICMR-National Institute of Nutrition, 500007, Hyderabad, India

    Kiran Alluri & Sudip Ghosh

  2. Drug Toxicology Division, ICMR-National Institute of Nutrition, 500007, Hyderabad, India

    Srinivasa Reddy Yathapu

  3. Microbiology and Immunology Division, ICMR-National Institute of Nutrition, 500007, Hyderabad, India

    Narendra Babu Kondapalli & Rajkumar Hemalatha

  4. Micronutrient Division, ICMR-National Institute of Nutrition, 500007, Hyderabad, India

    Krishna Madhavan Nair

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  1. Kiran Alluri
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Correspondence to Krishna Madhavan Nair or Sudip Ghosh.

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Alluri, K., Yathapu, S.R., Babu Kondapalli, N. et al. Levels of Zinc Transporters mRNA Depending on Zinc Status and HIV-1 Tat Induced Inflammation in Muscle (Rhabdomyosarcoma) and Monocyte (THP-1) Cell Lines. Biochemistry Moscow 86, 168–178 (2021). https://doi.org/10.1134/S000629792102005X

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