Redox signaling and oxidative stress: Cross talk with TNF-related apoptosis inducing ligand activity

Abstract

Redox regulation plays a key role in several physiopathological contexts and free radicals, from nitric oxide and superoxide anion up to other forms of reactive oxygen species (ROS), have been demonstrated to be involved in different biological and regulatory processes. The data reported in the current literature describe a link between ROS, inflammation and programmed cell death that is attracting interest as new pathways to be explored and targeted for therapeutic purposes. In this light, there is also growing attention to the involvement of this link in the activity of the TNF-related apoptosis inducing ligand (TRAIL). TRAIL is a member of the TNF ligands super family able to mediate multiple intracellular signals, with the potential to lead to a range of biological effects in different cell types. In particular, the hallmark of TRAIL is the ability to induce selective apoptosis in transformed cells leaving normal cells almost unaffected and this feature has already opened the door to several clinical studies for cancer treatment. Moreover, TRAIL plays a role in several physiological and pathological processes of both innate and adaptive immune systems and of the cardiovascular context, with a strong clinical potential. Nonetheless, several issues still need to be clarified about the signaling mediated by TRAIL to gain deeper insight into its therapeutic potential. In this light, the aim of this review is to summarize the main preclinical evidences about the interplay between TRAIL and redox signaling, with particular emphasis to the implications in vascular physiopathology and cancer.

A Fermented Whole Grain Prevents Lipopolysaccharides‐Induced Dysfunction in Human Endothelial Progenitor Cells

“…Accumulating evidence suggests an extensive crosstalk between ER stress, oxidative response, inflammatory cytokines, and apoptosis in cells. For instance, it has been described that CHOP, an ER stress-responsive transcription factor with apoptotic function, is involved in the inflammatory processes and plays crucial roles in the development and progression of atherosclerotic diseases [40, 41]. Furthermore, nuclear factors Nrf2 and Nrf1, two oxidative stress-induced transcription factors responsible for regulating the expression of many antioxidant genes, can also be activated by ER stress and UPR machinery to compensate stress condition, thus extending the crosstalk to include the activation of the antioxidant defense system [42].…”

Inflammation and Cardiovascular Cross Talk in Ischemic Vascular Diseases

“…The article of B. Toffoli et al addresses the role of two other cytokines belonging to the TNF family. Osteoprotegerin (OPG) and TNF-related apoptosis-inducing ligand (TRAIL) are two factors showing controversial effects on several physiopathological contexts [7, 8]. In a preclinical model, the authors show that dyslipidaemia and diabetes, two risk factors for cardiovascular disease, modify the vascular and cardiac expression of OPG and TRAIL leading to an increased OPG/TRAIL ratio.…”

Novel Polycondensed Partly Saturated β-Carbolines Including Ferrocene Derivatives: Synthesis, DFT-Supported Structural Analysis, Mechanism of Some Diastereoselective Transformations and a Preliminary Study of their In Vitro Antiproliferative Effects

“…On the other hand, synergistically strengthening the antiproliferative effects associated with selective binding-based classical targeted mechanisms of action, electron transfer processes via the Fenton pathway induced by redox active fragments, e.g., by suitably positioned ferrocenyl group(s) in the molecular scaffold, may play a key role in mitochondrial generation of reactive oxygen species (ROS), e.g., nitric oxide, superoxide anion and other forms of free radicals [12][13][14] that can be involved in biological regulatory processes finally leading to programmed cell death (apoptosis) [15]. Supporting the relevance of this view, convincing preclinical evidence about the interplay between particular binding-induced-and redox signalling pathways implicated in cancer has been disclosed [16]. Accordingly, due to their marked effects on malignant cell lines, a plethora of ferrocene derivatives with diverse molecular architectures have been emerged as potent antiproliferative agents in the last decades [17][18][19][20][21].…”