Trichostatin A enhances OGD-astrocyte viability by inhibiting inflammatory reaction mediated by NF-kappaB.
In this study we investigate the protective effects of Trichostatin A (TSA) on astrocyte injury after oxygen-glucose deprivation (OGD) and further explore its possible protective mechanisms of inhibiting inflammatory reaction mediated by nuclear factor-kappaB (NF-kappaB). In the in vitro model of astrocyte OGD, TSA treatment was used at different doses and time points before deprivation. Astroglial viability was determined by MTT assay. Then tumor necrosis factor-alpha, interleukin-1beta (IL-1beta), and IL-6 mRNA were measured by RT-PCR. Furthermore, the expression of phosphorylated p65, mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (ERK), MAPK/c-Jun N-terminal (JNK) and MAPK/p38 was assayed by Western blot. The results showed that TSA at the five doses (12.5, 25, 50, 100, and 200 ng/ml) significantly enhanced the astrocytes viability by 25.3%, 46.1%, 37.5%, 34.9%, and 22% of the vehicle, respectively. The level of TNF-alpha, IL-1beta and IL-6 mRNA in astrocytes was increased after OGD and down-regulated by TSA (p<0.05). In addition, the phosphorylation p65 was markedly activated in the astrocytes after OGD compared to the control (p<0.05). TSA inhibited phosphorylation of p65 but did not affect the MAPK pathway. Our results suggest that TSA protects astrocytes from damage after OGD by the inhibition of the inflammatory reaction and this protection is at least partially through the suppression of phosphorylation of NF-kappaB p65.
Niu
Fengnan
F
Department of Neurology, Drum Tower Hospital of Nanjing Medical University, PR China.
Zhang
Xin
X
Chang
Leilei
L
Wu
Jiayong
J
Yu
Yin
Y
Chen
Junhao
J
Xu
Yun
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D005947:Glucose / Q000172:deficiency; D006877:Hydroxamic Acids / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D020521:Stroke / Q000503:physiopathology*; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D002352:Carrier Proteins; D006877:Hydroxamic Acids; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D009363:Neoplasm Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C012589:trichostatin A; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose