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Biochemistry (Moscow). Papers in Press. Published on November 2, 2020 as Manuscript BM20-125.

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

K. Alluri1,a, S. Reddy Yathapu2,b, N. Babu Kondapalli3,c, Hemalatha R.3,d, K. P. M. Nair4,e*, and S. Ghosh1,f*

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

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

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

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

*To whom correspondence should be addressed.

Received June 1, 2020; Revised August 27, 2020; Accepted September 15, 2020
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.
KEY WORDS: zinc transporters, ZIPs, ZnTs, co-culture, HIV-1Tat, THP-1, RD