Clinical significance of EPHX2 deregulation in prostate cancer / 亚洲男科学杂志(英文版)

The arachidonic acid (AA) metabolic pathway participates in various physiological processes as well as in the development of malignancies. We analyzed genomic alterations in AA metabolic enzymes in the Cancer Genome Atlas (TCGA) prostate cancer (PCa) dataset and found that the gene encoding soluble epoxide hydrolase (EPHX2) is frequently deleted in PCa. EPHX2 mRNA and protein expression in PCa was examined in multiple datasets by differential gene expression analysis and in a tissue microarray by immunohistochemistry. The expression data were analyzed in conjunction with clinicopathological variables. Both the mRNA and protein expression levels of EPHX2 were significantly decreased in tumors compared with normal prostate tissues and were inversely correlated with the Gleason grade and disease-free survival time. Furthermore, EPHX2 mRNA expression was significantly decreased in metastatic and recurrent PCa compared with localized and primary PCa, respectively. In addition, EPHX2 protein expression correlated negatively with Ki67 expression. In conclusion, EPHX2 deregulation is significantly correlated with the clinical characteristics of PCa progression and may serve as a prognostic marker for PCa.

Raf/MEK/ERK1/2 signaling pathway and penile erection / 中华男科学杂志

Penile erection is regulated by the relaxation of corpus cavernosum smooth muscle cells (CCSMCs). It has been recognized that the Ras/MEK/ERK1/2 signaling pathway is closely related to the functions of CCSMCs and endothelial cells, and it is involved in the regulation of penile erection, mainly via phosphorylation of NO synthase. ERK1/2 phosphorylates, inhibits eNOS activity, and thus reduces the relaxation of CCSMCs and penile erection. But the site of phosphorylation is not yet clear. In CCSMCs and endothelial cells, the ERK1/2 pathway interacts with other cascades and regulates the erectile function of the penis. This article presents an overview of the researches on the ERK1/2 signaling cascade, its regulatory role and its interaction with other signaling pathways in penile erection.

Expressions of phospho-Erk1/2 and phospho-Akt1 in the corpus cavernosum of aged rats / 中华男科学杂志

<p><b>OBJECTIVE</b>Nitric oxide (NO) is a key factor for penile erection. Its generation is mainly regulated by nitric oxide synthase (NOS), while both phospho-Erkl/2 (P-Erkl/2) and phospho-Aktl (P-Aktl) can affect the expression and activity of NOS and consequently penile erection. This experiment aimed to study the expressions of P-Erkl/2 and P-Aktl in the corpus cavernosum and their possible roles in erectile dysfunction in aged rats.</p><p><b>METHODS</b>We included 10 two-month-old male SD rats in Group A and another 10 eighteen-month-old ones in Group B, measured the levels of serum testosterone, and detected the expressions of P-Erkl/2 and P-Aktl in the corpus cavernosum by immunohistochemistry and RT-PCR.</p><p><b>RESULTS</b>Compared with Group A, Group B showed a significantly decreased level of serum testosterone (9.57 +/- 1.57 nmol/L vs 4.73 +/- 0.94 nmol/L, P < 0.05), and remarkably increased mRNA expressions of P-Erk1 and P-Erk2 and protein expression of P-Erkl/2 (0.47 +/- 0.09, 0.61 +/- 0.11 and 7.50 +/- 1.81 vs 0.95 +/- 0.06, 0.92 +/- 0.05 and 32.09 +/- 8.45, P < 0.05). But there were no significant differences in the mRNA and protein expressions of P-Akt1 between the two groups (0.97 +/- 0.04 and 11.67 +/- 5.61 vs 0.94 +/- 0.05 and 10.93 +/- 3.06, P > 0.05).</p><p><b>CONCLUSION</b>The overexpression of P-Erk1/2 in the corpus cavernous may be one of the important mechanisms of aging-related erectile dysfunction.</p>

Expressions of phospho-Erk1/2 and phospho-Akt1 in the corpus cavernosum of spontaneous hypertensive rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To understand the expressions of phosphor Erk1/2 (P-Erk1/2) and phosphor Akt1 (P-Akt1) in the corpus cavernosum of spontaneous hypertensive (SH) and normotensive rats, and to investigate their relationship with penile erectile function.</p><p><b>METHODS</b>A series of electric stimuli were applied to the corpus cavernosum nerves of 8 SH rats, the changes of ICP/MAP observed continuously, and the expressions of P-Erk1/2 and P-Akt1 in the corpus cavernosum detected by immunohistochemistry and RT-PCR. Another 8 male WKY rats were taken as controls.</p><p><b>RESULTS</b>ICP/MAP was significantly lower in the SH rats than in the controls (P < 0.01). The mRNA expressions of P-Erk1 and P-Erk2 and the protein expression of P-Erk1/2 were significantly increased in the SH group (0.81 +/- 0.05, 0.91 +/- 0.06 and 54.22 +/- 10.05), as compared with 0.42 +/- 0.04, 0.68 +/- 0.14 and 7.05 +/- 1.45 in the WKY rats (P < 0.05). The mRNA and protein levels of P-Akt exhibited no significant differences between the SH and control groups (0.90 +/- 0.05 and 11.17 +/- 2.21 versus 0.92 +/- 0.06 and 10.91 +/- 1.86, P > 0.05).</p><p><b>CONCLUSION</b>Erectile dysfunction in hypertension patients is associated with the overexpression of P-Erk1/2 in the cavernous tissue, but not obviously correlated with the expression of P-Akt1.</p>

Expressions of Erk1/2 and PKB/Akt in the corpus cavernosum of castrated rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the expressions of Erk1/2 and PKB/Akt in the corpus cavernosum of castrated rats and investigate their action mechanism in the development of erectile dysfunction (ED) after castration.</p><p><b>METHODS</b>We randomly divided 20 eight-week-old SD rats into Groups A (sham-operation) and B (castration), and, 4 weeks after the operation, determined the level of serum testosterone (T) and the expressions of P-Erk1/2 and P-PKB/Akt proteins (integrated optical density/area, IA/area) and those of Erk1/2 and PKB/Akt mRNA (Marker: GAPDH) in the corpus cavernosum of the rats by immunohistochemical staining and RT-PCR.</p><p><b>RESULTS</b>Four weeks after the operation, the serum T level was significantly decreased in Group B in comparison with A ([10.090 +/- 3. 026] nmol/L versus [1.339 +/- 0.642] nmol/L, P < 0.05). Erk1/2 and PKB/Akt expressed in the corpus cavernosum of both groups of rats. The expressions of Erk1 and Erk2 mRNA and P-Erk1/2 were significantly higher in Group B (0. 840 +/- 0.062, 0.876 +/- 0.141 and 0.142 +/- 0.020) than in A (0.479 +/- 0.090, 0.599 +/- 0.100 and 0.119 +/- 0.029) (P < 0.05). But no statistically significant differences were found in the expressions of PKB/Akt mRNA and P-PKB/Akt between Groups B (0.974 +/- 0.040 and 0.164 +/- 0.036) and A (0.942 +/- 0.054 and 0.162 +/- 0.025) (P < 0.05).</p><p><b>CONCLUSION</b>Erk1/2 and PKB/Akt expressed in the penile tissues of both castrated and sham-operation rats. The increased expression of P-Erk1/2 in the corpus cavernosum may be involved in the development of ED in castrated rats.</p>