Apoptosis Overview Emphasizing the Role of Oxidative Stress, DNA Damage and Signal- Transduction Pathways

Abstract

Apoptosis (programmed cell death) is a central protective response to excess oxidative damage (especially DNA damage), and is also essential to embryogenesis, morphogenesis and normal immune function. An understanding of the cellular events leading to apoptosis is important for the design of new chemotherapeutic agents directed against the types of leukemias and lymphomas that are resistant to currently used chemotherapeutic protocols. We present here a review of the characteristic features of apoptosis, the cell types and situations in which it occurs, the types of oxidative stress that induce apoptosis, the signal-transduction pathways that either induce or prevent apoptosis, the biologic significance of apoptosis, the role of apoptosis in cancer, and an evaluation of the methodologies used to identify apoptotic cells. Two accompanying articles, demonstrating classic apoptosis and non-classic apoptosis in the same Epstein-Barr virus-transformed lymphoid cell line, are used to illustrate the value of employing multiple criteria to determine the type of cell death occurring in a given experimental system. Aspects of apoptosis and programmed cell death that are not covered in this review include histochemistry, details of cell deletion processes in the sculpting of tissues and organs in embryogenesis and morphogenesis, and the specific pathways leading to apoptosis in specific cell types. The readers should refer to the excellent books and reviews on the morphology, biochemistry and molecular biology of apoptosis already published on these topics. Emphasis is placed, in this review, on a proposed common pathway of apoptosis that may be relevant to all cell types.

Effects of age on DNA double-strand breaks and apoptosis in human sperm

“…Sakkas et al (22) have proposed that apoptosis is an event that is triggered early in spermatogenesis due to defects in cytoplasmic remodeling. However, cytoplasmic remodeling is unlikely to be a triggering event because apoptosis is considered to be initiated by DNA damage (49,77) or its misrepair (78). (80) have speculated that the presence of DNAse, after activation, can result in sperm-specific apoptotic degradation, although no caspases have been shown to be involved (44).…”

Excision repair cross-complementing 1 expression protects against ischemic injury following middle cerebral artery occlusion in the rat brain

“…[1][2][3] The accumulation of damaged DNA lesions results in cell death, due to various induced intracellular signaling pathways. [4][5][6] In addition, brain ischemia induces specific expression of genes related to the DNA repair pathway. Proliferating cell nuclear antigen (PCNA), which is required for DNA synthesis and nucleotide excision repair (NER), is upregulated in the CA3/dentate gyrus and downregulated in the vulnerable CA1 region following global ischemia.…”

The NAD+ precursors, nicotinic acid and nicotinamide protect cells against apoptosis induced by a multiple stress inducer, deoxycholate

“…Electron microscopy is the gold standard for the identification of apoptotic cells. 6,71,74,119 Ultrastructural features characteristic of apoptosis include condensation and margination of chromatin, fragmentation of the nucleus into double membrane-bound bodies, an increase in electron density, cytoplasmic vacuolization, normal appearing mitochondria, and apoptotic body formation.…”