Cinnamon polyphenols attenuate cell swelling and mitochondrial dysfunction following oxygen-glucose deprivation in glial cells.
Astrocyte swelling is an integral component of cytotoxic brain edema in ischemic injury. While mechanisms underlying astrocyte swelling are likely multifactorial, oxidative stress and mitochondrial dysfunction are hypothesized to contribute to such swelling. We investigated the protective effects of cinnamon polyphenol extract (CPE) that has anti-oxidant and insulin-potentiating effects on cell swelling and depolarization of the inner mitochondrial membrane potential (DeltaPsi(m)) in ischemic injury. C6 glial cells were subjected to oxygen-glucose deprivation (OGD) and cell volume determined using the 3-O-methyl-[3H]-glucose method at 90 min after the end of OGD. When compared with controls, OGD increased cell volume by 34%. This increase was blocked by CPE or insulin but not by blockers of oxidative/nitrosative stress including vitamin E, resveratrol, N-nitro-L-arginine methyl ester (L-NAME) or uric acid. Mitochondrial dysfunction, a key component of ischemic injury, contributes to cell swelling. Changes in DeltaPsi(m) were assessed at the end of OGD with tetramethylrhodamine ethyl ester (TMRE), a potentiometric dye. OGD induced a 39% decline in DeltaPsi(m) and this decline was blocked by CPE as well as insulin. To test the involvement of the mitochondrial permeability transition (mPT), we used Cyclosporin A (CsA), an immunosuppressant and a blocker of the mPT pore. CsA blocked cell swelling and the decline in DeltaPsi(m) but FK506, an immunosuppressant that does not block the mPT, did not. Our results show that CPE reduces OGD-induced cell swelling as well as the decline in DeltaPsi(m) in cultures and some of its protective effects may be through inhibiting the mPT.
Panickar
Kiran S
KS
Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, 10300 Baltimore Ave, Bldg 307C, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD 20705, USA. kiran.panickar@ars.usda.gov
Polansky
Marilyn M
MM
Anderson
Richard A
RA
D000818:Animals; D045744:Cell Line, Tumor; D048429:Cell Size / Q000187:drug effects; D002935:Cinnamomum zeylanicum / Q000737:chemistry*; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005910:Glioma / Q000473:pathology / Q000648:ultrastructure*; D005947:Glucose / Q000172:deficiency*; D000860:Hypoxia / Q000473:pathology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009569:Nitric Oxide / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols; D051381:Rats; D013997:Time Factors
D005419:Flavonoids; D007166:Immunosuppressive Agents; D007328:Insulin; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D009569:Nitric Oxide; D016572:Cyclosporine; D005947:Glucose