Apoptosis and Necrosis: Two Types of Cell Death in Alcoholic Liver Disease

Article excerpt

Heavy alcohol consumption over long periods of time can result in severe liver damage, including death of liver cells (i.e., hepatocytes). Two mechanismsapoptosis and necrosis-can contribute to hepatocyte death. In apoptosis, the affected cell actively participates in the cell death process, whereas in necrosis the cell death occurs in response to adverse conditions in the cell's environment. Numerous factors that may contribute to the initiation of hepatocyte apoptosis are affected by alcohol consumption. These factors include the enzyme cytochrome P450 2E1 (i.e., CYP2E1), small molecules (i.e., cytokines) involved in cell communication, oxidative stress, and changes in iron metabolism. Similarly, alcohol consumption can influence several factors believed to be involved in hepatocyte necrosis, including depletion of the energy-storing molecule adenosine-triphosphate, reduced oxygen levels (i.e., hypoxia) in the liver, oxidative stress, and bacterial molecules called endotoxins. KEY WORDS: alcoholic liver disorder; necrosis; cytolysis; hepatocyte; cytochrome P450; oxidation-reduction; iron; metabolic disorder; ATP (adenosine triphosphate); hypoxia; endotoxins; biochemical mechanism; pathogenesis; literature review

Many people who drink heavily over extended periods of time (i.e., several years) develop increasingly severe liver damage, including fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Fatty liver is caused by the accumulation of fat in the liver. Alcoholic hepatitis is characterized by extensive inflammation of the liver and the destruction of liver cells (i.e., hepatocytes). Moreover, scar tissue begins to form, replacing healthy liver tissue. In alcoholic cirrhosis, scarring and cell death progress further, resulting in distortion of the internal structure of the liver and, subsequently, in severe functional impairment and secondary failure of other organs, such as the kidney. These multiple complications can lead to the patient's death. By investigating the mechanisms underlying alcohol's deleterious effects on the liver, researchers hope to ultimately develop new diagnostic and therapeutic approaches to prevent these often fatal consequences of alcohol consumption.

Much recent research has focused on the mechanisms that contribute to hepatocyte death at the cellular level. Two processes play a role in hepatocyte destructionapoptosis and necrosis. This article briefly reviews the differences between these two processes and speculates on some of their underlying mechanisms. The article also discusses how heavy alcohol consumption may be associated with the mechanisms that promote these processes.

DIFFERENCES BETWEEN APOPTOSIS AND NECROSIS

Although the ultimate results of apoptosis and necrosis are the same (i.e., death of the affected cells), the two processes differ significantly. In apoptosis, the affected cells actively participate by activating a cascade of biochemical reactions that result in cell death. Accordingly, apoptosis has been called cell suicide (e.g., Rosser and Gores 1995).' In necrosis, however, cell death occurs because of adverse conditions or changes in the cell's environment. Thus, necrosis can be viewed as the consequence of a "biological accident" that leads to the death of an "innocent victim" (Rosser and Gores 1995).

Characteristic differences also exist in both the structure and the metabolic processes of cells that undergo apoptosis or necrosis (see figure, p. 325) (Rosser and Gores 1995). When a cell undergoes apoptosis, the entire cell, including the nucleus, separates into numerous fragments (i.e., apoptotic bodies). Simultaneously, the genetic material (i.e., DNA) of apoptotic cells breaks into a characteristic pattern of pieces of varying sizes. During the breakup of the cell, the cell continues to produce proteins and adenosine triphosphate (ATP), a molecule that is required for most of the cell's energy-consuming metabolic processes and which is essential for cell functioning. …