https://staff.blog.ui.ac.id/hsuryadi/files/2012/02/ROS_RNS.pdf

Free radicals and antioxidants in normal physiological functions and human disease

At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

/pdf/free-radicals-in-the-physiological-control-of-cell-function-g3w3iyr0ph.pdf

Free Radicals in the Physiological Control of Cell Function

Macrophages display remarkable plasticity and can change their physiology in response to environmental cues. These changes can give rise to different populations of cells with distinct functions. In this Review we suggest a new grouping of macrophage populations based on three different homeostatic activities - host defence, wound healing and immune regulation. We propose that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation. We characterize each population and provide examples of macrophages from specific disease states that have the characteristics of one or more of these populations.

/pdf/exploring-the-full-spectrum-of-macrophage-activation-b5rnrcgcen.pdf

Exploring the full spectrum of macrophage activation.

For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phag...

/pdf/the-nox-family-of-ros-generating-nadph-oxidases-physiology-zjc88zvh59.pdf

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

This review is directed at understanding how neuronal death occurs in two distinct insults, global ischemia and focal ischemia. These are the two principal rodent models for human disease. Cell dea...

Ischemic Cell Death in Brain Neurons

Nitric oxide and its role in apoptosis

Hypoxia inducible factor-1 (HIF-1) is the master regulator of metabolic adaptation to hypoxia. It is appreciated that HIF-1α accumulation is achieved under normoxic conditions by e.g., nitric oxide. We determined molecular mechanisms of HIF-1α accumulation under the impact of S-nitrosoglutathione (GSNO). In human embryonic kidney cells GSNO provoked nuclear accumulation of HIF-1α. This appeared unrelated to gene transcription and protein translation, thus pointing to inhibition of HIF-1α degradation. Indeed, GSNO as well as the hypoxia mimic CoCl2 decreased ubiquitination of HIF-1α and GSNO-induced HIF-1α failed to coimmunoprecipitate with pVHL (von Hippel Lindau protein). Considering that HIF-1α-pVHL interactions require prolyl hydroxylation of HIF-1α, we went on to demonstrate inhibition of HIF-1α prolyl hydroxylases (PHDs) by GSNO. In vitro HIF-1α-pVHL interactions revealed that GSNO dose-dependently inhibits PHD activity but not the interaction of a synthetic peptide resembling the hydroxylated oxygen-dependent degradation domain of HIF-1α with pVHL. We conclude that GSNO-attenuated prolyl hydroxylase activity accounts for HIF-1α accumulation under conditions of NO formation during normoxia and that PHD activity is subject to regulation by NO.

Nitric Oxide Impairs Normoxic Degradation of HIF-1α by Inhibition of Prolyl Hydroxylases

Tight regulation of inflammation is very important to guarantee a balanced immune response without developing chronic inflammation. One of the major mediators of the resolution of inflammation is the transcription factor: the nuclear factor erythroid 2-like 2 (Nrf2). Stabilized following oxidative stress, Nrf2 induces the expression of antioxidants as well as cytoprotective genes, which provoke an anti-inflammatory expression profile, and is crucial for the initiation of healing. In view of this fundamental modulatory role, it is clear that both hyper- or hypoactivation of Nrf2 contribute to the onset of chronic diseases. Understanding the tight regulation of Nrf2 expression/activation and its interaction with signaling pathways, known to affect inflammatory processes, will facilitate development of therapeutic approaches to prevent Nrf2 dysregulation and ameliorate chronic inflammatory diseases. We discuss in this review the principle mechanisms of Nrf2 regulation with a focus on inflammation and autophagy, extending the role of dysregulated Nrf2 to chronic diseases and tumor development.

Nrf2, the Master Regulator of Anti-Oxidative Responses

Nitric oxide (NO) is known for its diverse activities throughout biology Among signaling qualities, NO affects cellular decisions of life and death either by turning on apoptotic pathways or by shutting them off Although copious reports support both notions, the dichotomy of NO actions remains unsolved Proapoptotic pathways of NO are compatible with established signaling circuits appreciated for mitochondria-dependent roads of death, with some emphasis on the involvement of the tumor suppressor p53 as a target during cell death execution Antiapoptotic actions of NO are numerous, ranging from an immediate interference with proapoptotic signaling cascades to long-lasting effects based on expression of cell protective proteins with some interest on the ability of NO-redox species to block caspases by S-nitrosylation/S-nitrosation Summarizing emerging concepts to understand p53 accumulation on the one hand while proposing inhibition of procaspase processing on the other may help to define the pro- versus antiapoptotic roles of NO

/pdf/nitric-oxide-no-apoptosis-or-turning-it-on-4xry0tvv92.pdf

Bernhard Brüne

Papers

Nitric oxide and its role in apoptosis

Nitric Oxide Impairs Normoxic Degradation of HIF-1α by Inhibition of Prolyl Hydroxylases

Nrf2, the Master Regulator of Anti-Oxidative Responses

Nitric oxide: NO apoptosis or turning it ON?

Nitric oxide-induced S-glutathionylation and inactivation of glyceraldehyde-3-phosphate dehydrogenase.