Structural Biochemistry/Cell Signaling Pathways/Mobile Zinc and Nitric Oxide

Mobile zinc and the gaseous nitric oxide radical are two prominent examples of inorganic compounds that are found in many signaling pathways in living systems. To detect the presence of mobile zinc and nitric oxide, fluorescent probes is used. Fluorescent probes which are dyes that give off light when exposed to light, are excellent tools for detecting zinc and nitric oxide with high spatial and temporal resolution. To monitor biological processes in real time with high spatial resolution, using fluorescent imaging offers an excellent platform. It is known that fluorescent probes maintain good water solubility and membrane permeability.

1- Fluorescent Sensors For Mobile Zinc
The divalent zinc cation, Zn2+, influences a widely metabolic spectrum. Mobile zinc plays many physiological roles in zinc-enriched tissues, such as hippocampus, pancreas and prostate. Mobile zinc bioimaging is currently dominated by fluorescent probes. That is due to the technical advances in microscopy instruments and fluorescent sensors, which have been proved to be sensitive and versatile tools for zinc detection in living cells and tissues. In fluorescence microscopy experiments, zinc indicators depend on an increase or rarely a decrease in fluorescence emission intensity.

2- Fluorescent Sensors For Nitric Oxide
Nitric oxide is a free radical gas produced endogenously by a variety of mammalian cells. Nitric oxide plays various roles as the signal transmitter and it is involved in many physiological and pathological processes. Nitric oxide is synthesized from arginine by a complex reaction, while catalyzed by nitric oxide synthase. Nitric oxide synthase is an enzyme that catalyzes the conversion of l-arginine, NADPH, and oxugen to citrulline, nitric oxide and NADP+. There are two strategies in developing the small-moleculed fluorescent probes for nitric oxide. This strtegies are conducted by Pluth M.D et al. in their paper entitled, "Biochemistry of Mobile Zinc and Nitric Oxide Revealed by Fuorescent Sensors". The first is based on organic probes and they often result in bright emission enhancement in the presence of nitric oxide under aerobic conditions. this strategy is widely used. the second strategy is using transition metals to mediate reactivity of an emission dye with nitric oxide. it was found that these probes can be less bright than purely organic probes.

3- Interactions between Zinc and Nitirc Oxide

In “central nervous system”, Zinc and NO as well as their derivatives are essential inorganic species to make the system function well. Otherwise, “neurotoxic disease” may occur, such as “Alzheimer’s”, “Parkinson’s”, and “Huntington’s” diseases. When the “hippocampal neurons” are exposed under “NO donors” in an extent that beyond the nonneurotoxic level, Zn(Ⅱ)in brain tissue becomes more active and collective. As a result, more and more Zn(Ⅱ) accumulate in brain, leading to the increase of O2−, which finally causes the dysfunction of mitochondrial, the rise in ONOO−, as well as the change of the signaling pathway. Moreover, this process may also bring cells to death. By using the techniques of probes for NO and Zn, scientists might be able to understand the link between nitric oxides and zinc better and their quantitative properties on cell death.

Besides for their important roles in nervous system, zinc and nitric oxide also cooperate to defend diseases in the immune system. Less amount of zinc can weaken the immune system, while higher amount of NO can be caused by inflammation. By experiments, scientists have found out that adding 10 μM of Zn(Ⅱ) lowers the production of NO, which agrees with the anti-inflammatory property of Zn(Ⅱ).Therefore, the development in various fluorescent probes for zinc and nitric oxide will continuously help scientists explore how zinc and nitric oxides work in nervous, cardiovascular and immune system and also be applied into pathology field.

Reference

1. http://www.annualreviews.org/doi/full/10.1146/annurev-biochem-061009-091643?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed