Mechanisms of Adiponectin Action

The adipokine adiponectin is very concentrated in plasma, and decreased levels of adiponectin are associated with pathological conditions such as obesity, diabetes, cardiovascular diseases, and metabolic syndrome. When produced in its full-length form, adiponectin self-associates to generate multimeric complexes. The full-length form of adiponectin can be cleaved by the globular form of elastase that is produced locally, and the resulting biological effects are exerted in a paracrine or autocrine manner. The different forms of adiponectin bind to specific receptors consisting of two G-protein-independent, seven-transmembrane-spanning receptors, called AdipoR1 and AdipoR2, while T-cadherin has been identified as a potential receptor for high molecular weight complexes of adiponectin. Adiponectin exerts a key role in cellular metabolism, regulating glucose levels as well as fatty acid breakdown. However, its biological effects are heterogeneous, involving multiple target tissues. The Special Issue “Mechanisms of Adiponectin Action” highlights the pleiotropic role of this hormone through 3 research articles and 7 reviews. These papers focus on the recent knowledge regarding adiponectin in different target tissues, both in healthy and in diseased conditions

Oxidative Stress, Tumor Microenvironment, and Metabolic Reprogramming: A Diabolic Liaison

Conversely to normal cells, where deregulated oxidative stress drives the activation of death pathways, malignant cells exploit oxidative milieu for its advantage. Cancer cells are located in a very complex microenvironment together with stromal components that participate to enhance oxidative stress to promote tumor progression. Indeed, convincing experimental and clinical evidence underline the key role of oxidative stress in several tumor aspects thus affecting several characteristics of cancer cells. Oxidants influence the DNA mutational potential, intracellular signaling pathways controlling cell proliferation and survival and cell motility and invasiveness as well as control the reactivity of stromal components that is fundamental for cancer development and dissemination, inflammation, tissue repair, and de novo angiogenesis. This paper is focused on the role of oxidant species in the acquisition of two mandatory features for aggressive neoplastic cells, recently defined by Hanahan and Weinberg as new “hallmarks of cancer”: tumor microenvironment and metabolic reprogramming of cancer cells

Adiponectin Signaling Pathways in Liver Diseases

In the liver, adiponectin regulates both glucose and lipid metabolism and exerts an insulin-sensitizing effect. The binding of adiponectin with its specific receptors induces the activation of a proper signaling cascade that becomes altered in liver pathologies. This review describes the different signaling pathways in healthy and diseased hepatocytes, also highlighting the beneficial role of adiponectin in autophagy activation and hepatic regeneration

Redox Regulation of Nonmuscle Myosin Heavy Chain during Integrin Engagement

On the basis of our findings reporting that cell adhesion induces the generation of reactive oxygen species (ROS) after integrin engagement, we were interested in identifying redox-regulated proteins during this process. Mass spectrometry analysis led us to identify nonmuscle myosin heavy chain (nmMHC) as a target of ROS. Our results show that, while nmMHC is reduced in detached/rounded cells, it turns towards an oxidized state in adherent/spread cells due to the integrin-engaged ROS machinery. The functional role of nmMHC redox regulation is suggested by the redox sensitivity of its association with actin, suggesting a role of nmMHC oxidation in cytoskeleton movement. Analysis of muscle MHC (mMHC) redox state during muscle differentiation, a process linked to a great and stable decrease of ROS content, shows that the protein does not undergo a redox control. Hence, we propose that the redox regulation of MHC in nonprofessional muscle cells is mandatory for actin binding during dynamic cytoskeleton rearrangement, but it is dispensable for static and highly organized cytoskeletal contractile architecture in differentiating myotubes

Electrodynamic friction of a charged particle passing a conducting plate

The classical electromagnetic friction of a charged particle moving with prescribed constant velocity parallel to a planar imperfectly conducting surface is reinvestigated. As a concrete example, the Drude model is used to describe the conductor. The transverse electric and transverse magnetic contributions have very different character both in the low velocity (nonrelativistic) and high velocity (ultrarelativistic) regimes. Both numerical and analytical results are given. Most remarkably, the transverse magnetic contribution to the friction has a maximum for $|\mathbf{v}|<c$, and persists in the limit of vanishing resistivity for sufficiently high velocities. We also show how Vavilov-\v{C}erenkov radiation can be treated in the same formalism.Comment: 13 pages, 7 figures. This is the extensively revised version accepted by Physical Review Researc

Hyperglycemia and angiotensin II cooperate to enhance collagen I deposition by cardiac fibroblasts through a ROS-STAT3-dependent mechanism

AbstractCardiac fibroblasts significantly contribute to diabetes-induced structural and functional changes in the myocardium. The objective of the present study was to determine the effects of high glucose (alone or supplemented with angiotensin II) in the activation of the JAK2/STAT3 pathway and its involvement in collagen I production by cardiac fibroblasts. We observed that the diabetic environment 1) enhanced tyrosine phosphorylation of JAK2 and STAT3; 2) induced nuclear localization of tyrosine phosphorylated STAT3 through a reactive oxygen species-mediated mechanism, with angiotensin II stimulation further enhancing STAT3 nuclear accumulation; and 3) stimulated collagen I production. The effects were inhibited by depletion of reactive oxygen species or silencing of STAT3 in high glucose alone or supplemented with exogenous angiotensin II. Combined, our data demonstrate that increased collagen I deposition in the setting of high glucose occurred through a reactive oxygen species- and STAT3-dependent mechanism. Our results reveal a novel role for STAT3 as a key signaling molecule of collagen I production in cardiac fibroblasts exposed to a diabetic environment