Humanin (HN) and glucose transporter 8 (GLUT8) in pregnancies complicated by intrauterine growth restriction

宫内生长受限妊娠中的 Humanin (HN) 和葡萄糖转运蛋白 8 (GLUT8)

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作者:Carla Janzen, Margarida Y Y Lei, Il Seok D Jeong, Amit Ganguly, Peggy Sullivan, Vladislava Paharkova, Gina Capodanno, Hiromi Nakamura, Alix Perry, Bo-Chul Shin, Kuk-Wha Lee, Sherin U Devaskar

Background

Intrauterine growth restriction (IUGR)

Conclusions

There was elevated HN expression with cytoplasmic localization to EVTs on the maternal aspect of the human placenta affected by IUGR, also associated with increased GLUT8 expression. We found that while hypoxia increased both HN and GLUT8, serum deprivation increased HN expression alone. Also, a protein-protein interaction between HN and GLUT8 suggests that their interaction may fulfill a biologic role that requires interdependency. Future investigations delineating molecular interactions between these proteins are required to fully uncover their role in IUGR-affected pregnancies.

Results

We found 1) increased HN expression in human IUGR-affected pregnancies on the maternal aspect of the placenta (extravillous trophoblastic (EVT) cytoplasm) compared to control (i.e. appropriate for gestational age) pregnancies, and a concomitant increase in GLUT8 expression in the same compartment, 2) HN and GLUT8 showed a protein-protein interaction by co-immunoprecipitation, 3) elevated HN and GLUT8 levels in vitro under simulated hypoxia in human EVT cells, HTR8/SVneo, and 4) increased HN expression but attenuated GLUT8 expression in vitro under serum deprivation in HTR8/SVneo cells. Conclusions: There was elevated HN expression with cytoplasmic localization to EVTs on the maternal aspect of the human placenta affected by IUGR, also associated with increased GLUT8 expression. We found that while hypoxia increased both HN and GLUT8, serum deprivation increased HN expression alone. Also, a protein-protein interaction between HN and GLUT8 suggests that their interaction may fulfill a biologic role that requires interdependency. Future investigations delineating molecular interactions between these proteins are required to fully uncover their role in IUGR-affected pregnancies.

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