Damage to DNA and Proteins
المؤلف:
Vinay Kumar, MBBS, MD, FRCPath; Abul K. Abbas, MBBS; Jon C. Aster, MD, PhD
المصدر:
Robbins & Cotran Pathologic Basis of Disease
الجزء والصفحة:
10th E ,P 50
2025-10-18
100
Cells have mechanisms that repair damage to DNA, but if DNA damage is too severe to be corrected (e.g., after exposure to DNA damaging drugs, radiation, or oxidative stress), the cell initiates a suicide program that results in death by apoptosis. A similar reaction is triggered by improperly folded proteins, which may be the result of inherited mutations or acquired triggers such as free radicals. Because these mechanisms of cell injury typically cause apoptosis, they are discussed later in the chapter.
Reversible vs Irreversible Injury. Before concluding the discussion of the mechanisms of cell injury, it is useful to consider the possible events that determine when reversible injury becomes irreversible and progresses to cell death. The clinical relevance of this question is obvious—if we can answer it, we may be able to devise strategies for preventing cell injury from having permanent deleterious consequences. However, the molecular mechanisms connecting most forms of cell injury to ultimate cell death have proved elusive, for several reasons. The “point of no return,” at which the damage becomes irreversible, is still largely undefined, and there are no reliable morphologic or biochemical correlates of irreversibility. Two phenomena consistently characterize irreversibility—the inability to reverse mitochondrial dysfunction (lack of oxidative phosphorylation and ATP generation) even after resolution of the original injury, and profound disturbances in membrane function. As mentioned earlier, injury to lysosomal membranes results in the enzymatic dissolution of the injured cell that is characteristic of necrosis.
Leakage of intracellular proteins through the damaged cell membrane and ultimately into the circulation provides a means of detecting tissue-specific cellular injury and necrosis using blood serum samples. Cardiac muscle, for example, contains a specific isoform of the enzyme creatine kinase and of the contractile protein troponin; liver (and specifically bile duct epithelium) contains an isoform of the enzyme alkaline phosphatase; and hepatocytes contain transaminases. Irreversible injury and cell death in these tissues are reflected in increased levels of such proteins in the blood, and measurement of these biomarkers is used clinically to assess damage to these tissues.
الاكثر قراءة في مواضيع عامة في علم الامراض
اخر الاخبار
اخبار العتبة العباسية المقدسة
