title: Survival response of hippocampal neurons under low oxygen conditions induced by Hippophae rhamnoides is associated with JAK/STAT signaling.
abstract: Janus activated kinase/signal transducers and activators of transcription (JAK/STATs) pathway are associated with various neuronal functions including cell survival and inflammation. In the present study, it is hypothesized that protective action of aqueous extract of Hippophae rhamnoides in hippocampal neurons against hypoxia is mediated via JAK/STATs. Neuronal cells exposed to hypoxia (0.5% O2) display higher reactive oxygen species with compromised antioxidant status compared to unexposed control cells. Further, these cells had elevated levels of pro-inflammatory cytokines; tumor necrosis factor α and interleukin 6 and nuclear factor κappa B. Moreover, the expression of JAK1 was found to be highly expressed with phosphorylation of STAT3 and STAT5. Cells treated with JAK1, STAT3 and STAT5 specific inhibitors resulted in more cell death compared to hypoxic cells. Treatment of cells with extract prevented oxidative stress and inflammatory response associated with hypoxia. The extract treated cells had more cell survival than hypoxic cells with induction of JAK1 and STAT5b. Cells treated with extract having suppressed JAK1 or STAT3 or STAT5 expression showed reduced cell viability than the cell treated with extract alone. Overall, the findings from these studies indicate that the aqueous extract of Hippophae rhamnoides treatment inhibited hypoxia induced oxidative stress by altering cellular JAK1, STAT3 and STAT5 levels thereby enhancing cellular survival response to hypoxia and provide a basis for possible use of aqueous extract of Hippophae rhamnoides in facilitating tolerance to hypoxia.
authors: Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Delhi, India.
authors: Manimaran
authors: M
authors: Manickam
authors: Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Delhi, India.
authors: Rajkumar
authors: R
authors: Tulsawani
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000032:analysis; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000378:metabolism; D005419:Flavonoids / Q000032:analysis; D006624:Hippocampus / Q000473:pathology*; D031281:Hippophae / Q000737:chemistry*; D018836:Inflammation Mediators / Q000378:metabolism; D053613:Janus Kinase 1 / Q000235:genetics / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D010636:Phenols / Q000032:analysis; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000975:Antioxidants; D016207:Cytokines; D005419:Flavonoids; D018836:Inflammation Mediators; D016328:NF-kappa B; D010636:Phenols; D010936:Plant Extracts; D020011:Protective Agents; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D007770:L-Lactate Dehydrogenase; D053613:Janus Kinase 1; D053148:Caspase 3; D010100:Oxygen