Figure 1436

DNA fragmentation in apoptosis vs necrosis. DNA is made up of nucleosomal units. Each nucleosome of DNA is about 200 base pairs in size and is surrounded by histones. Between nucleosomes are small stretches of DNA that are not surrounded by histones and are called linker regions. During apoptosis, early activation of endonuclease(s) causes double-strand breaks in DNA between nucleosomes. No fragmentation occurs in nucleosomes because the DNA is "protected" by the histones. Because of the size of nucleosomes, the DNA is fragmented during apoptosis into multiples of 200 base pair pieces (eg, 200, 400, 600, 800). When the DNA of apoptotic cells is electrophoresed, a characteristic ladder pattern is found.

In contrast, necrosis is associated with the early release of lyzosomal proteases, which cause proteolysis of nuclear histones, leaving "naked" stretches of DNA not protected by histones. Activation of endonucleases during necrosis therefore cause DNA cleavage at multiple sites into double- and single-stranded DNA fragments of varying size. Electrophoresis of DNA from necrotic cells results in a smear pattern.

Loss of survival factors Deficiency of renal growth factors (eg, IGF-1, EGF, HGF) Loss of cell-cell and cell-matrix interactions Receptor-mediated activators of apoptosis Tumor necrosis factor Fas/Fas ligand Cytotoxic events Ischemia; hypoxia; anoxia Oxidant injury Nitric oxide Cisplati

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