Induction of endoplasmic reticulum stress in retinal pericytes by glucose deprivation.
Diabetic retinopathy is one of the major microvascular complications associated with diabetes mellitus, and the selective degeneration of retinal capillary pericytes is considered to be a hallmark of early retinopathy. Because glucose fluctuations commonly occur in diabetes, we hypothesized that these fluctuations will increase the endoplasmic reticulum (ER) stress and induce the unfolded protein response (UPR) in retinal pericytes. To study whether ER stress and the UPR can be induced in retinal pericytes, rat retinal capillary pericytes were cultured in different concentrations of glucose. Hypoglycemia but not hyperglycemia was found to activate UPR-specific enzymes in pericytes. Strong UPR activation leading to apoptosis was also observed when pericytes were cultured in glucose concentrations that were reduced from high to low or no glucose. These results indicate that induction of UPR is related not only to absolute concentrations but also to a shifting from higher to lower concentrations of glucose.
Ikesugi
Kengo
K
Department of Ophthalmology & Visual Sciences, University of Nebraska Medical Center, Omaha, NE 68198-5840, USA.
Mulhern
Michael L
ML
Madson
Christian J
CJ
Hosoya
Ken-Ichi
K
Terasaki
Tetsuya
T
Kador
Peter F
PF
Shinohara
Toshimichi
T
D051701:Activating Transcription Factor 4 / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D053454:Caspase 12 / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism; D007003:Hypoglycemia / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D018832:Molecular Chaperones / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D020286:Pericytes / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012171:Retinal Vessels / Q000166:cytology; D051742:Transcription Factor CHOP / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP
D051701:Activating Transcription Factor 4; D053454:Caspase 12; D005947:Glucose; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D051742:Transcription Factor CHOP; C497110:Atf4 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP