Cadmium-induced induction of cell death in human lens epithelial cells: implications to smoking associated cataractogenesis.
Cadmium is reported to accumulate in human eye tissues suggesting its implication in diverse ocular pathology. Using an in vitro cell culture model we investigated the effects of cadmium on human lens epithelial cells (HLECs) (HLE-B3). We observed cadmium-induced dose- as well as time-dependent decline in HLECs viability which was exacerbated significantly upon reduction of intracellular glutathione levels by buthionine sulfoximine (BSO). There was a dose-dependent significant increase in lactate dehydrogenase (LDH) release from HLECs suggesting cadmium-induced alteration of membrane integrity as well as necrotic cell death. The decline in cell viability was also due to apoptosis of the HLECs as determined by quantifying % apoptotic cells as well as PARP cleavage. Moreover, release of apoptosis inducing factor (AIF) into the cytosol was also detected. Cadmium was also observed to increase oxidative stress, lipid peroxidation and activation of MAPK pathway in HLECs. Antioxidants like N-acetylcysteine (NAC) and alpha-Tocopherol significantly prevented cadmium-induced toxicity in HLECs. Our findings suggest that cadmium-induced elevated oxidative stress as well as activation of MAPK signaling cascade eventually led to cell death of HLECs through apoptosis as well as necrosis. The loss of HLECs by cadmium could possibly explain its implication in cataract development particularly associated with smoking.
Kalariya
Nilesh M
NM
Department of Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555-1106, USA.
Nair
Bindu
B
Kalariya
Denish K
DK
Wills
Nancy K
NK
van Kuijk
Frederik J G M
FJ
D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity*; D002386:Cataract / Q000139:chemically induced / Q000209:etiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018384:Oxidative Stress; D015398:Signal Transduction / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects
D002104:Cadmium; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione