Apoptosis: pathophysiology of programmed cell death.

In all normal tissues, cell proliferation and cell death are balanced. The physiology of normal cell death, which has become generally known as apoptosis or programmed cell death, has been intensely investigated in recent years. In this review the cell biology and biochemistry of apoptosis are discussed. Although apoptotic cells can be morphologically recognized, characteristic molecular features such as internucleosomal DNA fragmentation, and histochemical techniques such as in situ end labeling, facilitate the recognition of apoptosis. Many of the genes involved in the regulation of apoptosis, which include cell growth associated genes such as c-myc and p53, have been identified. It has become clear that the bcl-genes (more explicitly bcl-2 and bax) are important apoptosis regulators. The details of the mechanism of programmed cell death are, however, not completely unraveled. It has become clear that apoptosis plays an important role in organ and tissue development during embryogenesis. Examples are the morphogenesis of limbs from limb buds, the development of the central nervous system and the maturation of the hematopoietic and lymphatic systems. Hormonal regulation of cells and tissues is also partly executed through apoptosis. In a variety of disease apoptosis plays a role. In cancer, apoptosis is a crucial feature, and in the resolution of inflammatory reactions, apoptosis is essential. In neurodegenerative diseases, dysregulation of the cell death programme may play a role. Further elucidation of the role of apoptosis in these diseases may lead to new possibilities for treatment.