ABSTRACT
Objective·To investigate the role of mitochondrial solute carrier family 25 member 13 (SLC25A13) on breast cancer development.Methods·SLC25A13 mRNA and protein expressions in invasive breast cancer tissues and normal breast tissues were from The Cancer Genome Atlas (TCGA) breast cancer dataset. Survival analysis was conducted online by Kaplan-Meier software. MCF-7 cell line was used for in vitro cell assay.Knockdown of SLC25A13 and sirtuin 2 (SIRT2) were conducted by siRNA transfection. Cell viability was measured with trypan blue exclusion. Cell cycle arrest was determined by flow cytometry. The mRNA expression of SLC25A13 and P27 were detected by quantitative PCR. The protein level of SLC25A13, P27 and SIRT2 were detected by Western blotting. Protein half-life of P27 was assessed by Western blotting after ycloheximide treatment. Results·SLC25A13 was up-regulated in invasive breast cancer tissues. High expression of SLC25A13 correlated with poor overall survival and breast cancer recurrence. SLC25A13 knockdown inhibited MCF-7 cell cycle progression. P27 and SIRT2 both accumulated after SLC25A13 knockdown. P27 accumulation resulted from prolonged protein half-life. Knockdown of SIRT2 restored cell cycle arrest as well as P27 accumulation caused by SLC25A13 silencing. Conclusion·High expression of SLC25A13 may promote cell cycle progression via SIRT2 in breast cancer development.
ABSTRACT
Spermatozoa are not mature until they transit the epididymis where they acquire motility and the ability to fertilize an egg through sequential modifications. The epididymis has three functional regions, caput, corpus, and cauda, and the luminal proteins of the epididymis play important roles in the above modifications. However, the proteins with differential enrichment between the caput and cauda are still largely unknown. To reveal the functions of the caput and cauda during sperm maturation, luminal proteins from caput and cauda of mice were analyzed by isobaric tag for relative and absolute quantitation (iTRAQ). Overall, 128 differentially enriched proteins were found, of which 46 were caput enriched and 82 were cauda enriched. Bioinformatic analysis showed that lipid metabolism was active in the caput; while anion- and cation-binding activity and phosphorus and organophosphate metabolism were active in the cauda. A new epididymal luminal protein, the caput-enriched PDZ domain containing 1 (Pdzk1), also named Na+/H+ exchange regulatory cofactor 3 (NHERF3), which plays a critical role in cholesterol metabolism and carnitine transport, was found in the lipid metabolism. Western blotting and immunofluorescence analyses showed that Pdzk1 was expressed in the epididymis but not in the testis, and localized at the middle piece of the sperm tail. Pdzk1 protein level was also reduced in the spermatozoa in case of asthenozoospermic patients compared with that in normozoospermic men, suggesting that Pdzk1 may participate in sperm maturation regulation and may be associated with male infertility. These results may provide new insights into the mechanisms of sperm maturation and male infertility.
ABSTRACT
Spermatozoa are not mature until they transit the epididymis where they acquire motility and the ability to fertilize an egg through sequential modifications. The epididymis has three functional regions, caput, corpus, and cauda, and the luminal proteins of the epididymis play important roles in the above modifications. However, the proteins with differential enrichment between the caput and cauda are still largely unknown. To reveal the functions of the caput and cauda during sperm maturation, luminal proteins from caput and cauda of mice were analyzed by isobaric tag for relative and absolute quantitation (iTRAQ). Overall, 128 differentially enriched proteins were found, of which 46 were caput enriched and 82 were cauda enriched. Bioinformatic analysis showed that lipid metabolism was active in the caput; while anion- and cation-binding activity and phosphorus and organophosphate metabolism were active in the cauda. A new epididymal luminal protein, the caput-enriched PDZ domain containing 1 (Pdzk1), also named Na+/H+ exchange regulatory cofactor 3 (NHERF3), which plays a critical role in cholesterol metabolism and carnitine transport, was found in the lipid metabolism. Western blotting and immunofluorescence analyses showed that Pdzk1 was expressed in the epididymis but not in the testis, and localized at the middle piece of the sperm tail. Pdzk1 protein level was also reduced in the spermatozoa in case of asthenozoospermic patients compared with that in normozoospermic men, suggesting that Pdzk1 may participate in sperm maturation regulation and may be associated with male infertility. These results may provide new insights into the mechanisms of sperm maturation and male infertility.
Subject(s)
Adult , Animals , Humans , Male , Mice , Asthenozoospermia/metabolism , Carrier Proteins/metabolism , Case-Control Studies , Epididymis/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins , Sperm Maturation , Sperm Tail/metabolism , Spermatozoa/metabolism , Testis/metabolismABSTRACT
Objective To explore the clinical features,maternal and fetal outcome in preeclampsia complications.(Methods)Clinical data of 86 cases of preeclampsia complications in heart,liver,kidney and brain were analyzed retrospectively.All the patients were divided into two groups: early onset preeclampsia(EOPE) group,36 cases,onset gestational weeks
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4.0 cm~2),slight group(2.5-4.0 cm~2),moderate group(1.5-2.5 cm~2)and severe group(