Role of ZnS Nanoparticles on Endoplasmic Reticulum Stress-mediated Apoptosis in Retinal Pigment Epithelial Cells.
Age-related macular degeneration (AMD) is the leading cause for irreversible visual impairment affecting 30-50 million individuals every year. Oxidative stress and endoplasmic reticulum stress have been identified as crucial factors for the pathogenesis of AMD. Current treatments do not focus on underlying stimuli responsible for the disease like AMD. Zinc is an important trace metal in retina and its deficiency leads to AMD. Recent studies on zinc sulphide nanoparticles (ZnS-NPs) are gaining attention in the field of physical and biological research. In this present study, in investigating the role of ZnS-NPs on hydrogen peroxide and thapsigargin-treated primary mice retinal pigment epithelial (MRPE) cells, we synthesized ZnS-NPs and characterized using atomic force microscope (AFM) and SEM-EDX. The ZnS-NPs abrogate the primary MRPE cell death through inhibition of oxidative stress-induced reactive oxygen species production and cell permeability. Oxidant molecules hydrogen peroxide and thapsigargin alter unfolded protein response such as glucose-regulated protein 78 (GRP78) and C/EBP homology protein (CHOP) expressions, whereas ZnS-NPs-pre-treated primary MRPE cells downregulated the overexpression of such proteins. The expressions of apoptotic proteins caspase 12 and cleaved caspase 9 and caspase 3 were also significantly controlled in ZnS-NPs-treated primary MRPE cells when comparing with thapsigargin- and hydrogen peroxide-treated cells. From these results, ZnS-NPs stabilize reactive oxygen species elevation, when subjected to hydrogen peroxide- and thapsigargin-mediated oxidant injury and helps in maintaining normal homeostasis through regulating endoplasmic reticulum (ER) stress response proteins which is the lead cause for apoptosis-mediated pathogenesis of AMD.
Department of Biotechnology, Kalasalingam University, Krishnankoil, Tamil Nadu, -626 126, India.
Bose
B
Karthikeyan
Department of Biotechnology, Kalasalingam University, Krishnankoil, Tamil Nadu, -626 126, India.
Arumugaperumal
A
Arun
Department of Biotechnology, Kalasalingam University, Krishnankoil, Tamil Nadu, -626 126, India.
Lakshminarasimhan
L
Harini
Department of Biotechnology, Kalasalingam University, Krishnankoil, Tamil Nadu, -626 126, India.|International Research Centre, Kalasalingam University, Krishnankoil, Tamil Nadu, -626 126, India.
Krishnan
K
Sundar
Department of Biotechnology, Kalasalingam University, Krishnankoil, Tamil Nadu, -626 126, India. t.kathiresan@klu.ac.in.|International Research Centre, Kalasalingam University, Krishnankoil, Tamil Nadu, -626 126, India. t.kathiresan@klu.ac.in.
Thandavarayan
T
Kathiresan
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000096:biosynthesis; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D051379:Mice; D053758:Nanoparticles / Q000032:analysis* / Q000648:ultrastructure; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology; D013440:Sulfides / Q000737:chemistry / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000096:biosynthesis; D017967:Zinc Compounds / Q000737:chemistry / Q000494:pharmacology*
C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D013440:Sulfides; D017967:Zinc Compounds; D051742:Transcription Factor CHOP; D020169:Caspases; C031238:zinc sulfide
CHOP; Caspase; GRP78; Mice retinal pigment epithelial cells; Reactive oxygen species; ZnS-NPs