An Insight on the Role of Nitric Oxide in Yeast Apoptosis of Curcumin-Treated Candida albicans.

Abstract

Nitric Oxide (NO) is a widely studied molecule due to its diverse biological functions. One of its activities, induction of apoptosis, is currently an area of active investigation in mammalian cells. However, there exists little information regarding the role of NO in yeast apoptosis. In an effort to investigate the mode of action by which NO induces programmed cell death in Candida albicans, we conducted a study on curcumin, a major bioactive compound, which is known as a potential apoptosis-inducing material due to several of its biological activities. First, NO generation was evaluated upon curcumin treatment. It is widely known that NO production is closely tied to cellular respiration, which is regulated by mitochondria. An increase in NO concentration leads to the inhibition of respiration and mitochondrial dysfunction. The hallmarks of mitochondrial dysfunction include a decrease in mitochondrial membrane potential along with increased mitochondrial mass, calcium concentration and ROS generation. A specific oxidative ROS compound, superoxide ([Formula: see text]), is strongly reactive with NO to form peroxynitrite (ONOO-). ONOO- disturbs intracellular redox levels, decreasing the overall ratio of glutathione (GSH). This leads to oxidative damage in C. albicans, triggering lethal DNA damage that eventually results in apoptosis. In the present study, a nitric oxide synthase (NOS) inhibitor, L-NG-Nitroarginine Methyl Ester (L-NAME), was used in each experiment. In all experiments, L-NAME pre-treatment of cells blocked the effects induced by curcumin, which indicates that nitric oxide is a component of the overall mechanism. In conclusion, NO account for an indispensable position in apoptosis of curcumin-treated C. albicans.