title: Protective Effect of Tempol on Buthionine Sulfoximine-Induced Mitochondrial Impairment in Hippocampal Derived HT22 Cells.
abstract: Using a simulated oxidative stress model of hippocampus-derived immortalized cell line (HT22), we report that prooxidant buthionine sulfoximine (BSO, 1 mM, 14 h), without adversely affecting cell viability or morphology, induced oxidative stress by inhibiting glutathione synthesis. BSO treatment also significantly reduced superoxide dismutase (SOD) activity (p < 0.05) and significantly lowered total antioxidant capacity (p < 0.001) in HT22 cells when compared to vehicle treated control cells. Antioxidant tempol, a piperidine nitroxide considered a SOD mimetic, reversed BSO-induced decline in SOD activity (p < 0.01) and also increased BSO-induced decline in total antioxidant capacity (p < 0.05). Interestingly, BSO treatment significantly reduced mitochondrial oxygen consumption (p < 0.05), decreased mitochondrial membrane potential (p < 0.05), and lowered ATP production (p < 0.05) when compared to vehicle treated control cells, collectively indicative of mitochondrial impairment. Antioxidant tempol treatment mitigated all three indicators of mitochondrial impairment. We postulate that BSO-induced oxidative stress in HT22 cells caused mitochondrial impairment, and tempol by increasing SOD activity and improving antioxidant capacity presumably protected the cells from BSO-induced mitochondrial impairment. In conclusion, present study provides an interesting simulation of oxidative stress in hippocampal cells, which will serve as an excellent model to study mitochondrial functions.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA.
authors.forename: Ankita
authors.initials: A
authors.lastname: Salvi
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Patki
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA.
authors.forename: Eisha
authors.initials: E
authors.lastname: Khan
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Asghar
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA.
authors.forename: Samina
authors.initials: S
authors.lastname: Salim
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D018696:Neuroprotective Agents; D013113:Spin Labels; D019328:Buthionine Sulfoximine; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase; D005978:Glutathione; C001803:tempol