[Interaction mechanism and influence between fatty acid oxidation in trophoblast cells and p38MAPK signal transduction pathway of severe preeclampsia].
OBJECTIVE
To investigate the effects of expression of mitochondria long-chain fatty acid oxidative enzyme (long-chain 3 hyroxyacyl CoA dehydrogenase, LCHAD) and p38 mitogen activated protein kinase (p38MAPK) signal transduction pathway in severe preeclampsia.


METHODS
Serum-free trophoblast cells cultured in vitro were stimulated by early onset severe preeclampsia serum (E-PE group), late onset severe preeclampsia serum (L-PE group), HELLP syndrome serum (HELLP group), and normal pregnancy serum (NP group) respectively; each group was added DMEM/F12 medium, reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor (NADPH-I) and p38MAPK inhibitor (p38-I) to stimulate cells. Expression of mRNA and protein of LCHAD in trophoblast cells were detected by real-time PCR and western blot.


RESULTS
(1)The expression of mRNA of LCHAD: the level of mRNA of LCHAD in NP+DMEM, E-PE+DMEM, E-PE+NADPH-I, E-PE+p38-I, L-PE+DMEM, L-PE+NADPH-I, L-PE+p38-I and HELLP+DMEM, HELLP+NADPH-I, HELLP+p38-I groups were 1.00 ± 0.03, 0.14 ± 0.08, 0.95 ± 0.20, 1.43 ± 1.02, 0.37 ± 0.18, 1.51 ± 0.36, 1.60 ± 0.31, 0.10 ± 0.04, 0.49 ± 0.10, 0.44 ± 0.21, respectively. The relative expressions of mRNA of LCHAD were significantly reduced in E-PE+DMEM, L-PE+DMEM and HELLP+DMEM groups compared with the NP+DMEM group (P < 0.05). Compared with the NP groups, the relative expressions of mRNA of LCHAD were significantly increased in L-PE+NADPH-I and L-PE+p38-I group (P < 0.05), while reduced in HELLP groups(P < 0.05). (2) The expression of protein of LCHAD: the relative expressions of protein of LCHAD in NP+DMEM, E-PE+DMEM, E-PE+NADPH-I, E-PE+p38-I, L-PE+DMEM, L-PE+NADPH-I, L-PE+p38-I and HELLP+ DMEM, HELLP+NADPH-I, HELLP+p38-I groups were 19.4 ± 2.2, 10.7 ± 1.1, 17.9 ± 3.3, 19.1 ± 2.9, 16.4 ± 2.3, 20.3 ± 2.3, 20.9 ± 4.3, 12.4 ± 2.3, 17.6 ± 2.6, 17.7 ± 2.0 respectively. Compared with the NP groups, the protein expressions of LCHAD were significantly remarkably reduced in E-PE+DMEM, L-PE+DMEM and HELLP groups (P < 0.05). Compared with the DMEM groups, the protein expressions of LCHAD were significantly increased in NADPH-I and p38-I groups of E-PE, L-PE and HELLP groups (P < 0.05).


CONCLUSIONS
These studies demonstrate that long chain fatty acid oxidation was involved in the pathogenesis and development of preeclampsia. The expressions of gene and protein of LCHAD were remarkably affected by early onset severe preeclampsia and HELLP syndrome. NADPH-I and p38-I may allay the disorder of fatty acid oxidation. p38MAPK signal transduction pathway may contributed in this process.
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
Xiao-le
XL
Sun
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China. Email: zi_yang@email.com.
Zi
Z
Yang
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
Wei
W
Wang
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
Xiao-ye
XY
Wang
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
Jia-lue
JL
Wang
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
Shu-ying
SY
Wu
D000328:Adult; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D017359:HELLP Syndrome / Q000097:blood / Q000378:metabolism; D006801:Humans; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011225:Pre-Eclampsia / Q000097:blood* / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D005227:Fatty Acids; D012333:RNA, Messenger; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; D019255:NADPH Oxidases; D048051:p38 Mitogen-Activated Protein Kinases