title: Nicotinamide inhibits Plasmodium falciparum Sir2 activity in vitro and parasite growth.
abstract: Plasmodium falciparum sirtuin, PfSir2, contains histone deacetylase (HDAC) activity that may be central to the regulation of virulence gene expression in the parasites. Although a few reports have been published recently regarding in vitro and in vivo function of PfSir2, expression of the endogenous protein (c. 30 kDa) has not been shown yet. Here we report the presence of PfSir2 in the parasite at the protein level by specific antibodies. HDAC activity of PfSir2 can be inhibited by nicotinamide, a product of sirtuin reaction. Surprisingly, we find that nicotinamide also delays parasite growth significantly in culture. These findings further our knowledge on PfSir2 and raise the possibility of using an inexpensive agent like nicotinamide as an antimalarial in combination with other antiparasitic drugs.
authors.affiliation: Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Dhaneswar
authors.initials: D
authors.lastname: Prusty
authors.forename: Parul
authors.initials: P
authors.lastname: Mehra
authors.forename: Sandeep
authors.initials: S
authors.lastname: Srivastava
authors.forename: Amol V
authors.initials: AV
authors.lastname: Shivange
authors.forename: Ashish
authors.initials: A
authors.lastname: Gupta
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Roy
authors.forename: Suman Kumar
authors.initials: SK
authors.lastname: Dhar
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan; D000962:Antimalarials; D016054:DNA, Protozoan; D056572:Histone Deacetylase Inhibitors; D009536:Niacinamide / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D037761:Sirtuins / Q000378:metabolism*
chemical_list: D000913:Antibodies, Protozoan; D000962:Antimalarials; D016054:DNA, Protozoan; D056572:Histone Deacetylase Inhibitors; D009536:Niacinamide; D037761:Sirtuins