Cyclosporine-A induces endoplasmic reticulum stress and influences pro-apoptotic factors in human gingival fibroblasts.
Cyclosporine-A (CsA) induces gingival overgrowth. Cyclosporine's anti-apoptotic activity in human gingival fibroblast is due to desensitization of mitochondrial permeability transition pore (MPTP) and augmentation of anti-apoptotic, Bcl2. Alternative mechanisms of apoptosis exist involving enzymes like calcium-dependent Calpain and signaling events related to apoptosis, like Glycogen synthase kinase 3β (GSK3β) and protein kinase A (PKA). Cyclosporine-A in renal tubular cells induces endoplasmic reticulum stress (ER stress) which has not been explored in gingival overgrowth. Hence, this study was carried out to assess the influence of Cyclosporine-on ER stress and on the alternate anti-apoptotic mechanisms. Human gingival fibroblasts were treated with CsA, and expression of ER stress markers, such as binding immunoglobulin protein and CCAAT/enhancer-binding protein homologous protein (CHOP), MPTP, and expression of Calpain & GSK3β /PKA were estimated. The results showed CsA-added fibroblast significantly increasing the expression of Endoplasmic reticulum stress markers. Contrary to usual ER stress outcome of apoptosis, we observed Cyclosporine's anti-apoptotic action in spite of augmented ER stress markers. We conclude that CsA's independent action on different organelles may alter the conventional outcome of ER stress.
Department of Periodontology and Implantology, Faculty of Dental Sciences & Centre for Regenerative Medicine and Stem Cell Research, Sri Ramachandra University, Porur, Chennai, India. Chennaidentist@gmail.com.
Suresh Ranga
SR
Rao
Department of Periodontology and Implantology, Faculty of Dental Sciences & Centre for Regenerative Medicine and Stem Cell Research, Sri Ramachandra University, Porur, Chennai, India.
Shiyamali
S
Sundararajan
Centre for Regenerative Medicine and Stem Cell Research, Central Research Facility, Sri Ramachandra University, Chennai, India.
Rajasekaran
R
Subbarayan
Centre for Indian Systems of Medicine Quality Assurance and Standardization, Central Research Facility, Sri Ramachandra University, Chennai, India.
Dinesh
D
Murugan Girija
D000328:Adult; D017209:Apoptosis; D002154:Calpain / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005881:Gingiva / Q000166:cytology*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D016572:Cyclosporine; D000071679:Glycogen Synthase Kinase 3 beta; D017868:Cyclic AMP-Dependent Protein Kinases; D002154:Calpain
Cyclosporine-A; ER Stress; Gingiva; Mitochondrial pore