Current Pharmaceutical Design - Volume 12, Issue 34, 2006

Apoptosis is a highly conserved form of cell death, orchestrated by an intricate cross talk between intracellular cysteine proteases (caspases) and amplification factors released from the inter-membranous space of the mitochondria, such as cytochrome C, apoptosis inducing factor, Smac/DIABLO, HtrA2/Omi, and others. Efficient execution of the apoptotic signal is controlled by diverse intracellular mechanisms, rangi Read More

Apoptosis is a genetically controlled and evolutionarily conserved form of cell death of critical importance for normal embryonic development and for the maintenance of tissue homeostasis in the adult organism. The malfunction of the death machinery may play a primary or secondary role in various diseases, with essentially too little or too much apoptosis leading to proliferative or degenerative diseases, respectively. The mac Read More

Reactive oxygen species (ROS) play a central role as second messengers in many signal transduction pathways, where they can post-translationally modify proteins via the oxidation of redox sensitive cysteine residues. The range of cellular processes under redox regulation is extensive and includes both the proliferative and apoptotic pathways. Control of the cellular redox environment is therefore essential for normal physi Read More

Nitric oxide (NO) is a small, highly reactive, diffusible free radical which has been implicated in many physiological and pathophysiological processes. It has either pro-apoptotic or anti-apoptotic effects on cells, depending upon a host of factors. This review outlines some of the regulatory molecules and organelles involved in the apoptotic pathways that can be influenced by the presence of NO, including p53, Bcl Read More

Apoptosis is an essential and highly conserved process for the maintenance of tissue homeostasis and involves a programmed series of events for the removal of effete, damaged, or mutated cells. Although, activation of caspases underscores the classical signaling cascade during apoptotic execution the role of caspase-independent mechanisms in apoptosis has also gained recognition. It is now well established that apoptoti Read More

Many cancer cells exhibit a disturbed intracellular redox balance, making them distinctively different from their 'healthy' counterparts. Some tumors, such as solid lung carcinoma, are hypoxic, and its cells are therefore more reducing than normal, while others, such as the ones of breast and prostate cancer, proliferate under oxidative stress (OS). These biochemical differences between normal and tumor tissue are signifi Read More

The permeability transition pore (PTPC), a polyprotein complex, participates in the mitochondrial homeostasis as well as in the mitochondrial phase of the intrinsic pathway of apoptosis. It integrates multiple death signals including alterations of the intracellular milieu, translocation of pro-apoptotic members of the Bax/Bcl-2 family, p53, and viral proteins. As a consequence, PTPC can act as a coordinator of the pro-apoptot Read More

G protein-activated inwardly rectifying K + (GIRK; Kir3) channels regulate the neuronal activity and heart rate. Molecular cloning of the GIRK channel genes has led to remarkable progress in our understanding of the molecular structure, distribution and functional modulation of these channels. Furthermore, the roles of GIRK channels in vivo have been shown by studies using GIRK knockout mice and weaver mutant mi Read More

After bacterial infection, the host reacts by signalling to the central nervous system where a cascade of physiologic, neuroendocrine and behavioural processes is orchestrated, collectively termed the acute phase response. Endotoxemia following Gram-negative bacterial infection induces a wide array of effects, including fever, loss of appetite and changes in gastrointestinal function that attempt to eliminate the ch Read More