Cadmium-induced stress: a close look at the relationship between autophagy and apoptosis.

Stress is acknowledged as one of the major factors responsible for autophagy induction, a tightly regulated process that acts as a pro-death or pro-survival mechanism within cells. Cadmium (Cd), a toxic heavy metal, induces apoptosis and autophagy in cells after exposure to low concentrations. This is due to Cd's ability to induce oxidative stress in cells and tissues by overproducing reactive oxygen species. Several proteins have been found to mediate the process of autophagy but aspects of their specific roles and targets remain undefined. Though LC3-II and p62 have traditionally been used as biomarkers that define autophagy, recent findings have revealed some limitations to LC3-II because it can be accumulated in cells in an autophagy-independent manner, whereas p62 remains a good determinant of the process. In addition to LC3-II and p62, recent studies have suggested that a new member of the autophagy protein family, the vacuole membrane protein 1 (VMP1), is essential in driving autophagy and could be an important biomarker for detecting the initiation and progression of autophagy. This review therefore focuses on current trends in autophagy biomarkers, the effect of Cd on the expression of LC3-II, p62, VMP1, and Beclin-1 and their relation and inter-regulatory roles in autophagy and apoptosis, pharmacological importance, and the mechanisms involved.