H2S protects hippocampal neurons from anoxia-reoxygenation through cAMP-mediated PI3K/Akt/p70S6K cell-survival signaling pathways.
The study aims to investigate the effect of hydrogen sulfide (H(2)S) on the phosphatidylinositol 3-kinase (PI3K)/Akt/p70 ribosomal S6 kinase (p70S6K) signal transduction pathway after oxygen glucose deprivation/reoxygenation (OGD/R) in the rat hippocampus. Newborn Wister rats were decapitated under anesthesia, and hippocampal tissue was dissected. Cells were plated at 1.0 × 10(5) cells/mL on polylysine-treated 96-well and 6-well plates. After 7 days in culture, cells were randomly assigned to six groups: control, OGD/R, sodium hydrosulfide (NaHS) following OGD/R, NaHS/triciribine following OGD/R, NaHS/rapamycin following OGD/R, and NaHS/triciribine/rapamycin following OGD/R. Neuronal purity and cell viability were assessed in each group, as well as apoptosis and expression of cyclic adenosine 3', 5'-monophosphate (cAMP), PI3K, Akt, and p70S6K. NaHS enhanced cAMP concentration and expression of PI3K, Akt, and p70S6K. In addition, neuronal viability was increased and apoptotic neuronal numbers decreased (P<0.01). Triciribine inhibited Akt and p70S6K, as well as decreased cell survival and viability compared with the NaHS group (P<0.05 or P<0.01). Rapamycin resulted in decreased p70S6K expression and neuronal viability, as well as increased number of apoptotic neurons compared with the NaHS group (P<0.05 or P<0.01). H(2)S acted via cAMP-mediated PI3K/Akt/p70S6K signal transduction pathways to inhibit hippocampal neuronal apoptosis and protect neurons from OGD/R-induced injury.
Shao
Jian-Lin
JL
Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical College, Kunming, Yunnan, 650032, China.
Wan
Xiao-Hong
XH
Chen
Yan
Y
Bi
Chun
C
Chen
Hong-Mei
HM
Zhong
Ying
Y
Heng
Xin-Hua
XH
Qian
Jin-Qiao
JQ
D000393:Air Pollutants / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D000393:Air Pollutants; D000242:Cyclic AMP; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D006862:Hydrogen Sulfide