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bioRxiv · 10.1101/2022.06.09.495418

Sphingosine-1-phosphate regulates Plasmodium histone deacetylase activity and exhibits epigenetic control over cell death and differentiation

singh, s.·Sah, R. K.·Anand, S.·Kumari, G.·Saini, M.·Hada, R. S.·Madan, E.·Gupta, A.
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Abstract

Histone deacetylases (HDACs) play a key role in cellular processes by the regulation of gene transcription. This study contributes a novel insight how Plasmodium falciparum HDAC (PfHDAC-1) is regulated by S1P produced by host erythrocyte SphK-1. The binding of S1P with endogenous nuclear extract PfHDAC-1 and recombinant PfHDAC-1 blocks their activity. A significant modulation in transcriptional regulation of P. falciparum HDAC regulated genes resulted upon inhibition of S1P production through blocking of hSphK-1 by clinical SphK-1 inhibitor PF-543. PF-543 led to profound decrease in S1P in the parasites nuclear fraction. The significant modulation of PfHDAC-1 regulated specific candidate genes related to gametocytogenesis, virulence and proliferation was observed in parasite treated with SphK-1 inhibitor, suggesting S1P targets PfHDAC-1 and participates in epigenetic regulation of these key cellular processes. The epigenetic modulation of parasite cell growth and differentiation by host provides a novel approach for the developmenthost-targeted therapeutics.

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singh, s., Sah, R. K., Anand, S., Kumari, G., Saini, M., Hada, R. S., Madan, E., Gupta, A.. 2022-06-09. Sphingosine-1-phosphate regulates Plasmodium histone deacetylase activity and exhibits epigenetic control over cell death and differentiation. https://doi.org/10.1101/2022.06.09.495418

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