Hemin protects against oxygen-glucose deprivation-induced apoptosis activation via neuroglobin in SH-SY5Y cells.
This study aimed to investigate the mechanism underlying the neuroprotective effect of hemin in oxygen-glucose deprivation (OGD)-treated neurons. OGD-treated SH-SY5Y cells (human neuroblastoma cells) were used in the study. The cellular viability of SH-SY5Y cells was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the cell apoptosis rate was determined by flow cytometry analysis with Annexin V-fluorescein isothiocyanate and propidium iodide staining with or without hemin pretreatment. Cell viability and apoptotic activation were detected after hemin administration combined with neuroglobin (Nqb), thioredoxin-1, peroxiredoxin-2, or heme oxygenase-1 siRNA transient transfection. The release of cytochrome c from mitochondria and the interaction between Ngb and cytochrome c were examined with hemin pretreatment. Hemin had a neuroprotective effect in OGD-treated SH-SY5Y cells, which was mainly mediated by the upregulation of Ngb. Moreover, the release of cytochrome c from mitochondria was inhibited by hemin-induced Ngb expression through facilitating the interaction of Ngb with cytochrome c in mitochondria. The present findings provided new insights into the neuroprotective mechanisms of hemin. It was concluded that low-dose hemin pretreatment had a neuroprotective effect in OGD-treated SH-SY5Y cells, through inhibiting cell apoptosis. The neuroprotective effects of hemin following hypoxic-ischemic neuronal damage were mainly mediated by Ngb. One underlying mechanism was hemin-induced overexpression of mitochondrial Ngb, which inhibited endogenous apoptosis via the association with cytochrome c.
Department of Intensive Care Unit, Xiangya Hospital, Central South University, No 87, Xiangya Road, Changsha, 410008, China.
Yun-Jia
YJ
Wang
Department of Intensive Care Unit, Xiangya Hospital, Central South University, No 87, Xiangya Road, Changsha, 410008, China.
Qian-Yi
QY
Peng
Department of Intensive Care Unit, Xiangya Hospital, Central South University, No 87, Xiangya Road, Changsha, 410008, China.
Song-Yun
SY
Deng
Department of Intensive Care Unit, Xiangya Hospital, Central South University, No 87, Xiangya Road, Changsha, 410008, China.
Cai-Xia
CX
Chen
Department of Intensive Care Unit, Xiangya Hospital, Central South University, No 87, Xiangya Road, Changsha, 410008, China.
Long
L
Wu
Department of Intensive Care Unit, Xiangya Hospital, Central South University, No 87, Xiangya Road, Changsha, 410008, China.
Li
L
Huang
Department of Intensive Care Unit, Xiangya Hospital, Central South University, No 87, Xiangya Road, Changsha, 410008, China. zln7095@126.com.
Li-Na
LN
Zhang
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005914:Globins / Q000096:biosynthesis*; D005947:Glucose / Q000172:deficiency*; D006427:Hemin / Q000494:pharmacology*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D000078787:Neuroglobin; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*
D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D018696:Neuroprotective Agents; D006427:Hemin; D005914:Globins; D005947:Glucose
Hemin; Neuroglobin; Neuroprotection; Oxygen–glucose deprivation; SH-SY5Y