Abstract
Cadmium (Cd) is a common environmental pollutant that can damage many organs and the fetus. We previously reported that Cd induced apoptosis in primary rat osteoblasts (OBs). OB apoptosis induced by Cd will eventually lead to osteoporosis. In this study, a novel pharmacotherapeutic approach was investigated involving the regulation of autophagy to prevent Cd osteoporosis. The results showed that Cd treatment induced apoptosis in OBs, as demonstrated by the ratio of Bax/Bcl-2, activation of poly (ADP-ribose) polymerase (PARP) and nuclear condensation. In addition, cells treated with Cd were observed to undergo autophagic cell death by monitoring the induction of the beclin 1, autophagy gene 5 (Atg5) and the expression of microtubule-associated protein 1 light chain 3 (LC3). The results indicated that promotion of apoptotic cell death by Cd is accompanied by induction of autophagy in OBs. Interestingly, Cd-mediated apoptotic cell death was suppressed by pretreatment with the autophagy activator rapamycin (RAP) and potentiated by the autophagy inhibitor chloroquine (CQ) or small interfering RNA against beclin 1. These findings suggest that the autophagic response plays a protective role that impedes eventual cell death. Activation of autophagy could therefore be an adjunctive strategy for treatment of Cd-induced osteoporosis.
Highlights
Cadmium is a toxic heavy metal used widely in industries that can enter the environment and stay intact for long periods of time
OBs incubated with Cd (1, 2 and 5 μ M) for 3 h showed the same regulation of expression of Bcl-2, Bax and cleaved poly (ADP-ribose) polymerase (PARP) dose-dependently (Fig. 1D–F)
Previous studies on Cd have focused on chronic low Cd exposure, mainly from dietary sources, which damages organ function and human health, rather than acute, lethal exposure[35]
Summary
Cadmium is a toxic heavy metal used widely in industries that can enter the environment and stay intact for long periods of time. We investigated the mechanism of Cd-induced apoptosis in OBs. Autophagy, or type II programmed cell death, is a major intracellular degradation process that delivers cytoplasmic constituents to the lysosome[16]. Many studies have demonstrated that Cd exposure induces activation of autophagy in diverse cell types[19,20,21], few have clarified the mechanism of autophagy induced by Cd in primary rat OBs. Apoptosis, autophagy and necrosis are different processes of cell death. Primary OBs were used as a model to investigate the role of autophagy in apoptosis induced by Cd, which may allow future discoveries of novel drug targets for Cd toxicity treatment
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