Oxidative stress and muscle homeostasis

Purpose of review The term oxidative stress is often used to indicate a condition in which the accumulation of reactive oxygen species is considered just damaging. We will discuss both the physiological and pathological role of oxidative stress on skeletal muscle homeostasis and function, and how oxidative stress can activates opposite signaling molecule to regulate gene and protein expression to guarantee muscle adaptation and to trigger a pathological condition. Recent findings Emerging evidences have assigned a critical role to oxidative stress in muscle homeostasis and in the physiopathology of skeletal muscle, suggesting that reactive oxygen species are not merely damaging agent inflicting random destruction to the cell structure and function, but useful signaling molecules to regulate growth, proliferation, differentiation, and adaptation, at least within physiological concentration. Summary The role of oxidative stress on muscle homeostasis is quite complex. It is clear that transiently increased levels of oxidative stress might reflect a potentially health promoting process, whereas an uncontrolled accumulation of oxidative stress might have pathological implication. Additional work is, therefore, necessary to understand and define precisely whether the manipulation of the redox balance represents a useful approach in the design of therapeutic strategies for muscle diseases.PURPOSE OF REVIEW: The term oxidative stress is often used to indicate a condition in which the accumulation of reactive oxygen species is considered just damaging. We will discuss both the physiological and pathological role of oxidative stress on skeletal muscle homeostasis and function, and how oxidative stress can activates opposite signaling molecule to regulate gene and protein expression to guarantee muscle adaptation and to trigger a pathological condition. RECENT FINDINGS: Emerging evidences have assigned a critical role to oxidative stress in muscle homeostasis and in the physiopathology of skeletal muscle, suggesting that reactive oxygen species are not merely damaging agent inflicting random destruction to the cell structure and function, but useful signaling molecules to regulate growth, proliferation, differentiation, and adaptation, at least within physiological concentration. SUMMARY: The role of oxidative stress on muscle homeostasis is quite complex. It is clear that transiently increased levels of oxidative stress might reflect a potentially health promoting process, whereas an uncontrolled accumulation of oxidative stress might have pathological implication. Additional work is, therefore, necessary to understand and define precisely whether the manipulation of the redox balance represents a useful approach in the design of therapeutic strategies for muscle diseases

Anchored phosphatases modulate glucose homeostasis.

Endocrine release of insulin principally controls glucose homeostasis. Nutrient-induced exocytosis of insulin granules from pancreatic β-cells involves ion channels and mobilization of Ca(2+) and cyclic AMP (cAMP) signalling pathways. Whole-animal physiology, islet studies and live-β-cell imaging approaches reveal that ablation of the kinase/phosphatase anchoring protein AKAP150 impairs insulin secretion in mice. Loss of AKAP150 impacts L-type Ca(2+) currents, and attenuates cytoplasmic accumulation of Ca(2+) and cAMP in β-cells. Yet surprisingly AKAP150 null animals display improved glucose handling and heightened insulin sensitivity in skeletal muscle. More refined analyses of AKAP150 knock-in mice unable to anchor protein kinase A or protein phosphatase 2B uncover an unexpected observation that tethering of phosphatases to a seven-residue sequence of the anchoring protein is the predominant molecular event underlying these metabolic phenotypes. Thus anchored signalling events that facilitate insulin secretion and glucose homeostasis may be set by AKAP150 associated phosphatase activity

Risk homeostasis in information security:challenges in confirming existence and verifying impact

The central premise behind risk homeostasis theory is that humans adapt their behaviors, based on external factors, to align with a personal risk tolerance level. In essence, this means that the safer or more secure they feel, the more likely it is that they will behave in a risky manner. If this effect exists, it serves to restrict the ability of risk mitigation techniques to effect improvements.The concept is hotly debated in the safety area. Some authors agree that the effect exists, but also point out that it is poorly understood and unreliably predicted. Other re-searchers consider the entire concept fallacious. It is important to gain clarity about whether the effect exists, and to gauge its impact if such evidence can indeed be found.In this paper we consider risk homeostasis in the context of information security. Similar to the safety area, information security could well be impaired if a risk homeostasis effect neutralizes the potential benefits of risk mitigation measures. If the risk homeostasis effect does indeed exist and does impact risk-related behaviors, people will simply elevate risky behaviors in response to feeling less vulnerable due to following security procedures and using protective technologies.Here we discuss, in particular, the challenges we face in confirming the existence and impact of the risk homeostasis effect in information security, especially in an era of ethical research practice

METTL3 regulates WTAP protein homeostasis

The Wilms tumor 1 (WT1)-associated protein (WTAP) is upregulated in many tumors, including, acute myeloid leukemia (AML), where it plays an oncogenic role by interacting with different proteins involved in RNA processing and cell proliferation. In addition, WTAP is also a regulator of the nuclear complex required for the deposition of N6-methyladenosine (m6A) into mRNAs, containing the METTL3 methyltransferase. However, it is not clear if WTAP may have m6A-independent regulatory functions that might contribute to its oncogenic role. Here, we show that both knockdown and overexpression of METTL3 protein results in WTAP protein upregulation, indicating that METTL3 levels are critical for WTAP protein homeostasis. However, we show that WTAP upregulation is not sufficient to promote cell proliferation in the absence of a functional METTL3. Therein, these data indicate that the reported oncogenic function of WTAP is strictly connected to a functional m6A methylation complex

Intestinal stem cell proliferation and epithelial homeostasis in the adult Drosophila midgut

Adult tissue homeostasis requires a tight balance between the removal of old or damaged cells and the production of new ones. Such processes are usually driven by dedicated stem cells that reside within specific tissue locations or niches. The intestinal epithelium has a remarkable regenerative capacity, which has made it a prime paradigm for the study of stem cell-driven tissue self-renewal. The discovery of the presence of stem cells in the adult midgut of the fruit fly Drosophila melanogaster has significantly impacted our understanding of the role of stem cells in intestinal homeostasis. Here we will review the current knowledge of the main mechanisms involved in the regulation of tissue homeostasis in the adult Drosophila midgut, with a focus on the role of stem cells in this process. We will also discuss processes involving acute or chronic disruption of normal intestinal homeostasis such as damage-induced regeneration and ageing

Homeostasis as the Mechanism of Evolution.

Homeostasis is conventionally thought of merely as a synchronic (same time) servo-mechanism that maintains the status quo for organismal physiology. However, when seen from the perspective of developmental physiology, homeostasis is a robust, dynamic, intergenerational, diachronic (across-time) mechanism for the maintenance, perpetuation and modification of physiologic structure and function. The integral relationships generated by cell-cell signaling for the mechanisms of embryogenesis, physiology and repair provide the needed insight to the scale-free universality of the homeostatic principle, offering a novel opportunity for a Systems approach to Biology. Starting with the inception of life itself, with the advent of reproduction during meiosis and mitosis, moving forward both ontogenetically and phylogenetically through the evolutionary steps involved in adaptation to an ever-changing environment, Biology and Evolution Theory need no longer default to teleology

Integrative concept of homeostasis: translating physiology into medicine

To truly understand living systems they must be viewed as a whole. In order to achieve this and to come to some law to which living systems obey, data obtained on cells, tissues and organs should be integrated. Because there are no such laws yet, there is usually a long path for physiological findings obtained by reductionist approaches to be translated into medical practice. The concept and accompanying equations of homeostasis presented here are aimed to develop biological laws and to bridge this gap between physiology and medicine. The concept of homeostasis takes into account energy input and output, enlisting all relevant contributors. In homeostasis, input should equal the output. What I suggest here is that if the system is out of homeostasis, the homeostasis may be regained by changing any of the input or output components in an adequate manner, not only the one that has changed first. The proposed equation should enable for new lab findings regarding any pathophysiological conditions to find a more direct use in medicine. It should also ease ‘decision making’ in medicine and make therapy development and treatment outcome more straightforward and predictable. Finally, to recognize the basic laws of living systems enables for evolutionary adaptations and processes to be understood better