Cadmium-induced apoptotic death of human retinal pigment epithelial cells is mediated by MAPK pathway

Nilesh M. Kalariya, Nancy K. Wills, Kota Ramana, Satish Srivastava, Frederik J G M van Kuijk

Research output: Contribution to journalArticle

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Abstract

Cadmium (Cd), released from cigarette smoke and metal industrial activities, is known to accumulate in human body organs including retina and is particularly higher in retinal tissues of age-related macular degeneration (AMD) eyes compared to non-AMD eyes. We have determined the cytotoxic effects of Cd on human retinal pigment epithelial (RPE) cells. Upon Cd treatment, there was a dose- and time-dependent decline in ARPE-19 cell viability as well as early apoptotic changes such as altered mitochondrial membrane potential (MMP) and Cytochrome C release in cytosol. Depletion of GSH by buthionine-[S,R]-sulfoximine (BSO) resulted in increased Cd toxicity in ARPE-19 cells. Cadmium also caused reactive oxygen species (ROS) generation and activation of mitogen-activated protein kinases (MAPKs) pathway including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (Erk1/2), and p38 in ARPE-19 cells. Antioxidants such as N-acetylcysteine (NAC) significantly reduced Cd-induced toxicity. These results indicate that elevated ROS-induced activation of the MAPK signaling pathway could be associated with Cd-induced RPE cell apoptosis, one of the major contributing factors in AMD. The toxic effects of Cd on ARPE-19 cells indicate that environmental heavy metals such as Cd could be important potential factors in RPE cells death associated retinal diseases particularly related to smoking.

Original languageEnglish (US)
Pages (from-to)494-502
Number of pages9
JournalExperimental Eye Research
Volume89
Issue number4
DOIs
StatePublished - Oct 2009

Fingerprint

Retinal Pigments
Mitogen-Activated Protein Kinases
Cadmium
Epithelial Cells
Macular Degeneration
Reactive Oxygen Species
Retinal Diseases
Mitogen-Activated Protein Kinase 3
JNK Mitogen-Activated Protein Kinases
Mitochondrial Membrane Potential
Poisons
Mitogen-Activated Protein Kinase 1
Acetylcysteine
Cytochromes
Heavy Metals
Human Body
Smoke
Tobacco Products
Cytosol
Retina

Keywords

  • AMD
  • apoptosis
  • cadmium
  • MAPK
  • oxidative stress
  • retinal pigment epithelium

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Cadmium-induced apoptotic death of human retinal pigment epithelial cells is mediated by MAPK pathway. / Kalariya, Nilesh M.; Wills, Nancy K.; Ramana, Kota; Srivastava, Satish; van Kuijk, Frederik J G M.

In: Experimental Eye Research, Vol. 89, No. 4, 10.2009, p. 494-502.

Research output: Contribution to journalArticle

Kalariya, Nilesh M. ; Wills, Nancy K. ; Ramana, Kota ; Srivastava, Satish ; van Kuijk, Frederik J G M. / Cadmium-induced apoptotic death of human retinal pigment epithelial cells is mediated by MAPK pathway. In: Experimental Eye Research. 2009 ; Vol. 89, No. 4. pp. 494-502.
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