Cellular homeostasis

Ruvolo PP Ceramide regulates cellular homeostasis via diverse stress signaling pathways. Leukemia 2001 15 1153. 

A typical dose-response is shown in Fig. 11.1. This assumes that a dose exists which has no effects due to the capacity of the body to reverse minor changes and maintain cellular homeostasis. The threshold dose is normally taken to be the observed experimental NOAEL, but the NOAEL could be lower than the threshold dose. The NOAEL chosen is the one that represents the most sensitive species studied since all international protocols require that the chemical is tested on at least two species (frequently the rat and the mouse). 

The maintenance of cellular homeostasis involves a balance of cell division, differentiation, senescence, and apoptosis. 

Micronutrients are required to support metabolic activities for cellular homeostasis such as enzyme reactions, fluid balance, and regulation of electrophysiologic processes. 

The continual development and evolution of novel and powerful technologies has allowed scientists to answer increasingly complex questions about the basic mechanisms underlying cellular homeostasis for the benefit of human health. Our understanding of how cells proliferate, thrive, adapt, and die in response to numerous environmental... 

Figure 11.1 The basic concepts of Ca2+ cellular homeostasis and signalling. (From Carafoli, 2004. Copyright 2004, with permission from Elsevier.)...

Reversible acetylation of histone and nonhistone proteins play key role in maintaining cellular homeostasis. In this following section we shall discuss about the physiological significances of acetylation and deacetylation of different classes of nonhistone proteins. 

Figure 3. Role of nonhistone protein acetylation in maintaining cellular homeostasis- mis-regulation and disease connection (a) Acetylation of nonhistone proteins are associated with active or repressed chromatin architecture as guided by suitable cellular signals for maintenance of gene expression. Misreg-ulation of HAT function leads to diseased state, where chromatin architecture is altered than under normal condition. In a parallel way the posttranslational modification status of these proteins may act as versatile tool to diagnose the various stages of disease manifestation e.g. probable involvement of acetylated NPMl modulating its stress response function can lead us to use it as a marker for various disease states, (b) Acetylation of nonhistone proteins in connection to diseases like Cancer, AIDS, Diabetes and others. (See Colour Plate 14.)...

The epigenetic codes set by HATs are countered by the activity of the histone deacetylases. This delicate balance has been documented to maintain the cellular homeostasis. HDACs seem to play dual opposing roles in disease manifestation. Dysfunctioning of HDACs are involved in several cancers. In some cases HDACs... 

Since the discovery of the first histone demethylase in 2004, a number of demethy-lases have been identified and implicated in the control of gene expression programs and cell fate decisions. The cellular functions of histone demethylases are only beginning to be deciphered, but many of these enzymes have nevertheless been found to play biologically important roles. Histone demethylases are linked to the regulation of for example stem cell self-renewal, differentiation, proliferation and hormone-dependent responses. These processes are critical for development and cellular homeostasis and their deregulation is implicated in pathological disorders. 

Hypoxia is a deficiency of oxygen needed to maintain cellular homeostasis. It may be caused by a reduction in blood supply, namely ischemia, decreased cardiopulmonary function, and diminished oxygen-carrying capacity of the blood. Subsequent oxygen deficiency in tissues leads to depressed aerobic metabolism and, thus, insufficient ATP synthesis. Reductions in blood flow also exacerbate oxygen deprivation by impairing delivery of nutrients, such as glucose, and the removal of metabolic wastes, such as C02, from affected cells. 

The total number of neurons in the adult brain does not dramatically increase, and cell death is an established process in the adult brain. Newly-generated neuronal cells may contribute to cellular homeostasis. The disequilibrium in cellular homeostasis may result in neurodegenerative diseases. 

Other strategies include detailed studies of the changes in brain carbohydrate metabolism in ageing and how this may differ in patients with Alzheimer s disease. Changes in the composition and biophysical properties of neuronal membranes may also be of crucial importance in regulating the cytosolic free calcium, which could affect cellular homeostasis. 

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