Pigment-epithelium-derived factor down regulates hyperglycemia-induced apoptosis via PI3K/Akt activation in goat retinal pericytes.
Pigment epithelium-derived factor (PEDF) is a well-known protease inhibitor for angiogenesis in the eye, suggesting that loss of PEDF in eye is implicated in the pathogenesis of proliferative diabetic retinopathy. Since the role of PEDF in diabetic retinopathy is unclear, the effect of PEDF on different types of cells constituting the blood vessel has to be checked. Here, we have investigated the effects of PEDF under hyperglycemic conditions in retinal pericytes, isolated from goat's eye and used to analyze the signaling pathway involved. High glucose increased the apoptotic cell death and intracellular reactive oxygen species generation, which was blocked on the addition of PEDF. PEDF was found to inhibit the apoptotic cell death and protect the cells via activating the PI3K/Akt pathway, which was analyzed with dominant negative Akt and constitutively active Akt-transfected cells. These results demonstrate that PEDF protects pericytes against the high glucose-induced apoptosis and dysfunction.
Haribalaganesh
Ravinarayanan
R
Department of Biotechnology, Division of Molecular and Cellular Biology, Kalasalingam University, Anand Nagar, Krishnankoil, Viruthunagar, Tamilnadu, India.
Sheikpranbabu
Sardarpasha
S
Elayappan
Banumathi
B
Venkataraman
Deepak
D
Gurunathan
Sangiliyandi
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005136:Eye Proteins / Q000502:physiology*; D005799:Genes, Dominant; D005947:Glucose / Q000494:pharmacology*; D006041:Goats; D009414:Nerve Growth Factors / Q000502:physiology*; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000502:physiology*; D020286:Pericytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012171:Retinal Vessels / Q000166:cytology*; D015843:Serpins / Q000502:physiology*; D000099174:Pigment Epithelium-Derived Factor
D053148:Caspase 3; D005136:Eye Proteins; D005947:Glucose; D009414:Nerve Growth Factors; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor