Apoptosis and Its Role in Human Disease

Abstract

In a landmark paper published over two decades ago, Kerr et al. proposed the term apoptosis "for a hitherto little recognized mechanism of controlled cell deletion, which appears to play a complementary but opposite role to mitosis in the regulation of animal cell populations". In the ensuing years, this natural cell death process was studied at the basic science level, primarily with a view to understanding its roles in cancer and in the development and maintenance of the immune system. More recently, however, evidence has suggested a role for the failure of normal apoptosis control in many of the major diseases of the industrialized world. Though complex, apoptosis appears amenable to therapeutic intervention. The range of modern pharmaceutical strategies available to treat such disregulated gene-directed processes offers promise for advances in the control of cancer, immune system and neurodegenerative disorders, heart disease, and perhaps even the aging process itself.

Tissue expression and subcellular localization of the pro-survival molecule Bcl-w

“…All constructs were verified by automated sequencing (ABI Perkin Elmer). The vector pQE-9 Bcl-w was constructed by subcloning the full-length human bcl-w gene inframe with the N-terminal (His) 6 tag in pQE-9 (Qiagen). Recombinant (His) 6 -tagged Bcl-w protein was produced in SG13009 [ P REP 4] cells and purified on a nickel column according to the manufacturer's protocols (Qiagen).…”

“…1,2 Failure of cells to undergo appropriate apoptosis can lead to cellular transformation 3 or autoimmunity, 4,5 whereas premature apoptosis of long-lived cells has been implicated in the pathology of degenerative disorders. 6 Cell death can be induced under a variety of physiological and experimentally induced conditions. These cytotoxic stimuli can activate distinct signaling pathways that converge upon a common cell death effector machinery driven by cysteine proteases (caspases).…”

Mitochondrial implication in apoptosis. Towards an endosymbiont hypothesis of apoptosis evolution

“…In mammalian cells, such apoptotis-triggering stimuli include numerous toxins, suboptimal culture conditions, interventions on second messenger systems, and litigation of certain receptors (Fas/ APO-1/CD95, TGF-R, TNF-R, etc.) or, in the case of obligate growth factor receptor, the absence of receptor occupancy (Barr and Tomei, 1994;Kroemer, 1995;Kroemer et al, 1995;Thompson, 1995;Wertz and Hanley, 1996). In spite of the striking heterogeneity of apoptosis induction pathways, some characteristics of the apoptotic process are near-to-constant and do not depend on the induction protocol.…”

Expression of the Fas-ligand gene in ejaculated sperm from adolescents with and without varicocele

“…On the other hand, excessive death signals may lead to decimation of germ cells, and thus, to altered spermatogenesis and male infertility. Excessive testicular apoptosis in varicocele has also been previously reported [48].…”