PMID- 29423002 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1943-8141 (Print) IS - 1943-8141 (Electronic) IS - 1943-8141 (Linking) VI - 10 IP - 1 DP - 2018 TI - NDUFA4 enhances neuron growth by triggering growth factors and inhibiting neuron apoptosis through Bcl-2 and cytochrome C mediated signaling pathway. PG - 164-174 AB - Dandy-Walker malformation (DWM) is the most prevalent congenital malformation in cerebellum, however, pathological mechanism of DWM has not been fully clarified. This study aims to investigate effects of NDUFA4 on growth of neurons. LV5-NDUFA4 and LV3-NDUFA4-RNAi lentivirus were constructed and transfected to neurons. Ciclosporin A, together with the two lentivirus were applied to neurons to observe neuron growth, apoptosis, and related protein expression. MTT assay was used to observe neuron growth. Apoptosis was detected by using flow cytometry assay. Real-time PCR was utilized to examine NDUFA4 mRNA expression. Western blot and immunohistochemistry assay were used to detect nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), brain fibroblast growth factor (bFGF) and cytochrome C (Cyt C) expression. Results indicated that NDUFA4 significantly enhanced neuron activity and inhibited neuron apoptosis (P<0.05). NDUFA4 significantly increased Bcl-2 and decreased cleave caspase-3 expression compared to normal control group (P<0.05). NDUFA4 up-regulated growth factors, including NGF, BDNF, bFGF and Cyt C and inhibited Cyt C expression. NDUFA4 interfere inhibits antagonistic effect of ciclosporin A on apoptosis and decrease up-regulative effect of ciclosporin A on neuron growth. NDUFA4 over-expression enhances antagonistic effect of ciclosporin A on apoptosis and increases up-regulative effect of ciclosporin A on neuron growth. In conclusion, NDUFA4 enhances neuron growth by triggering NGF, BDNF and bFGF expression, inhibits neuron apoptosis by increasing Bcl-2 expression and decreasing cyto C expression. Meanwhile, NDUFA4 regulates the antagonistic effect of ciclosporin A on apoptosis and the up-regulative effect of ciclosporin A on neuron growth. FAU - Fu, Fang AU - Fu F AD - Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical UniversityGuangzhou 510623, Guangdong, China. FAU - Li, Yan AU - Li Y AD - Guangzhou Umbilical Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical UniversityGuangzhou 510623, Guangdong, China. FAU - Li, Ru AU - Li R AD - Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical UniversityGuangzhou 510623, Guangdong, China. FAU - Lei, Ting-Ying AU - Lei TY AD - Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical UniversityGuangzhou 510623, Guangdong, China. FAU - Wang, Dan AU - Wang D AD - Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical UniversityGuangzhou 510623, Guangdong, China. FAU - Yang, Xin AU - Yang X AD - Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical UniversityGuangzhou 510623, Guangdong, China. FAU - Han, Jin AU - Han J AD - Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical UniversityGuangzhou 510623, Guangdong, China. FAU - Pan, Min AU - Pan M AD - Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical UniversityGuangzhou 510623, Guangdong, China. FAU - Zhen, Li AU - Zhen L AD - Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical UniversityGuangzhou 510623, Guangdong, China. FAU - Ou, Yan-Mei AU - Ou YM AD - Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical UniversityGuangzhou 510623, Guangdong, China. FAU - Li, Jian AU - Li J AD - Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical UniversityGuangzhou 510623, Guangdong, China. FAU - Li, Fao-Tao AU - Li FT AD - Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical UniversityGuangzhou 510623, Guangdong, China. FAU - Jing, Xiang-Yi AU - Jing XY AD - Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical UniversityGuangzhou 510623, Guangdong, China. FAU - Li, Dong-Zhi AU - Li DZ AD - Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical UniversityGuangzhou 510623, Guangdong, China. FAU - Liao, Can AU - Liao C AD - Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical UniversityGuangzhou 510623, Guangdong, China. LA - eng PT - Journal Article DEP - 20180115 PL - United States TA - Am J Transl Res JT - American journal of translational research JID - 101493030 PMC - PMC5801355 OTO - NOTNLM OT - Dandy-Walker malformation OT - NDUFA4 gene OT - apoptosis OT - ciclosporin A OT - growth factor COIS- None. EDAT- 2018/02/10 06:00 MHDA- 2018/02/10 06:01 PMCR- 2018/01/15 CRDT- 2018/02/10 06:00 PHST- 2017/03/28 00:00 [received] PHST- 2017/07/28 00:00 [accepted] PHST- 2018/02/10 06:00 [entrez] PHST- 2018/02/10 06:00 [pubmed] PHST- 2018/02/10 06:01 [medline] PHST- 2018/01/15 00:00 [pmc-release] PST - epublish SO - Am J Transl Res. 2018 Jan 15;10(1):164-174. eCollection 2018.