World Journal of
Pharmaceutical and Life Sciences

HEPATIC APOPTOSIS: BASIC MOLECULAR CONCEPTS AND MECHANISMS

Tarekegn Gebreyesus Abisso*, Yao Mawulikplimi Adzavon*, Pengxiang Zhao*, Xujuan Zhang, Xin Zhang, Mengyu Liu, Limin Wang and Xuemei Ma

ABSTRACT

Elimination of unwanted, injured or diseased cells by apoptosis is the requirement for the maintenance of homeostasis and regulation of physiological functions in multicellular organisms. Because of its exceptional role and anatomical position, liver is susceptible to exogenous xenobiotics and toxins, and highly vulnerable to tissue apoptosis. Apoptosis, which is accompanied by biochemical features such as DNA fragmentation, membrane alterations, and degradation of liver cells can be initiated by extrinsic or intrinsic pathways by means of death signals from the cell exterior. The extrinsic pathway is activated by the binding of a group of transmembrane receptors (death receptors) to their related ligands. Some of the death receptors in liver comprise Fas or CD95, Tumor TNF-R1, TRAIL-R2 also called death receptor 4 and 5 (DR4 and DR5). The intrinsic pathway usually activates apoptosis through members Bcl-2 family, which control mitochondrial outer membrane permeabilization, cytochrome C release, and consequently caspase initiation. Caspases are a family of aspartate-specific cysteinyl proteases that are triggered during and assist the execution of apoptosis in liver cells. A group of caspases that are triggered first in the process (upstream) are called initiation caspases, while others that bring the important structural hits of apoptosis are called executioner caspases. Caspases, that is, caspase -2, -8, -9, and -10, belong to the group of initiator caspases, while caspases, that is, caspase- 3, -6, and -7, belong to the group of executioner enzymes. Any malfunctioning in the course of liver apoptosis might result in various kinds of liver disorders from auto-immune diseases to the high risk hepatocellular carcinoma (liver cancer). In this review, we addressed some common molecular concepts and mechanisms of hepatic apoptosis and circumstances that are linked to hepatic apoptosis.

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