Cell death features induced in Leishmania major by 1,3,4-thiadiazole derivatives.

Abstract:

:Under a variety of stress conditions, Leishmania species display some morphological and biochemical features characteristic of mammalian programmed cell death or necrosis. Nitroheteroaryl-1,3,4-thiadiazoles induce cell death in Leishmania major (L. major). Putative mechanisms of action of these compounds were investigated in vitro at cellular and molecular levels. We used colorimetric assay to measure acid phosphatase activity which is an indicator of cell viability in the promastigotes. The mode of toxicity was determined by detection of phosphatidylserine translocation to the surface, evaluation of cell membrane integrity, and in situ dUTP nick end-labeling assay. We also determined poly-ADP-ribose polymerase-like protein (PARP) level in the parasites after treatment. A significant reduction of acid phosphatase level, one of the most crucial and virulent factors of the parasite was found in parasites treated with 1,3,4-thiadiazole derivatives. In addition, 1,3,4-thiadiazole derivatives induced loss of plasma membrane integrity, DNA breakage, proteolysis of PARP and necrotic-like death in the parasites.

journal_name

Exp Parasitol

authors

Ardestani SK,Poorrajab F,Razmi S,Foroumadi A,Ajdary S,Gharegozlou B,Behrouzi-Fardmoghadam M,Shafiee A

doi

10.1016/j.exppara.2012.06.002

subject

Has Abstract

pub_date

2012-10-01 00:00:00

pages

116-22

issue

2

eissn

0014-4894

issn

1090-2449

pii

S0014-4894(12)00189-0

journal_volume

132

pub_type

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