Effects of polyamine synthesis enzymes on angiogenesis and apoptosis during endometriosis

Objectives: Since we assumed that endometriosis is a benign cell division disorder, our study was conducted to investigate the effects of the relationships between polyamine synthesis and angiogenesis in the formation of endometriosis. Material and methods: Thirty-five patients with endometriosis and 35 healthy female women were included in the study. The patient and the control groups were compared regarding the blood levels of agmatine, argininecarboxylase (ADC), ornithinecarboxylase (ODC), agmatinase, arginase, ornithine, and the vascular endothelial growth factor (VEGF). Results: There is a statistically significant difference between the patient and the control groups regarding the agmatinase, arginase and VEGF levels (higher in the patient group) (p 0.05). There is a statistically significant difference between the patient and the control groups regarding the agmatine levels (higher in the control group) (p < 0.05). Conclusions: The increase in the serum levels of polyamine synthesis enzymes may contribute to the formation of endometriosis. It is anticipated that the study of the relationship between enzymes and molecules in the polyamine synthesis pathway and angiogenesis in patients with endometriosis will contribute to the literature.

angiogenesisapoptosisendometriosispolyamine

- Gerner EW, Meyskens FL. Polyamines and cancer: old molecules, new understanding. Nat Rev Cancer. 2004; 4(10): 781–792. - MOINARD C, CYNOBER L, DEBANDT J. Polyamines: metabolism and implications in human diseases. Clinical Nutrition. 2005; 24(2): 184–197. - Thomas T, Thomas TJ. Polyamines in cell growth and cell death: molecular mechanisms and therapeutic applications. Cell Mol Life Sci. 2001; 58(2): 244–258. - Jeevanandam M, Petersen SR. Clinical role of polyamine analysis: problem and promise. Curr Opin Clin Nutr Metab Care. 2001; 4(5): 385–390. - Seiler N. Catabolism of polyamines. Amino Acids. 2004; 26(3): 217–233. - Li Li, Rao J, Guo X, et al. Polyamine depletion stabilizes p53 resulting in inhibition of normal intestinal epithelial cell proliferation. American Journal of Physiology-Cell Physiology. 2001; 281(3): C941–C953. - Liang M, Ekblad E, Hellstrand P, et al. Polyamine synthesis inhibition attenuates vascular smooth muscle cell migration. J Vasc Res. 2004; 41(2): 141–147. - Hoet P, Nemery B. Polyamines in the lung: polyamine uptake and polyamine-linked pathological or toxicological conditions. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2000; 278(3): L417–L433. - Ray R, Viar M, Yuan Q, et al. Polyamine depletion delays apoptosis of rat intestinal epithelial cells. American Journal of Physiology-Cell Physiology. 2000; 278(3): C480–C489. - Williams K. Interactions of polyamines with ion channels. Biochem J. 1997; 325 ( Pt 2): 289–297. - Pfeffer LM, Yang CH, Murti A, et al. Polyamine depletion induces rapid NF-kappa B activation in IEC-6 cells. J Biol Chem. 2001; 276(49): 45909–45913. - Shearer JD, Richards JR, Mills CD. Differantial regulation of macrophage arginine metabolism: a proposed role in wound healing. Am J Physiol. 1997; 272(35): E181–E190. - Feng Y, Halaris A, Piletz J. Determination of agmatine in brain and plasma using high-performance liquid chromatography with fluorescence detection. Journal of Chromatography B: Biomedical Sciences and Applications. 1997; 691(2): 277–286. - Yang Y, Yuan Y, Ma X, et al. Ca2+ channel subunit a 1D inhibits endometriosis cell apoptosis and mediated by prostaglandin E2. Ginekol Pol. 2019; 90(12): 669–674. - Munksgaard PS, Blaakaer J. The association between endometriosis and ovarian cancer: a review of histological, genetic and molecular alterations. Gynecol Oncol. 2012; 124(1): 164–169. - Gökmen SS, Yörük Y, Cakir E, et al. Arginase and ornithine, as markers in human non-small cell lung carcinoma. Cancer Biochem Biophys. 1999; 17(1-2): 125–131. - Leu SY, Wang SR. Clinical significance of arginase in colorectal cancer. Cancer. 1992; 70(4): 733–736, doi: 10.1002/1097-0142(19920815)70:43.0.co;2-6. - Harris BE, Pretlow TP, Bradley Jr EL, et al. Arginase activity in prostatic tissue of patients with benign prostatic hyperplasia and prostatic carcinoma . Cancer Res. 1983; 43(6): 3008–3012. - Löser C, Fölsch U, Paprotny C, et al. Polyamine Concentrations in Pancreatic Tissue, Serum, and Urine of Patients with Pancreatic Cancer. Pancreas. 1990; 5(2): 119–127. - Gökmen SS, Aygit AC, Ayhan MS, et al. Significance of arginase and ornithine in malignant tumors of the human skin. J Lab Clin Med. 2001; 137(5): 340–344. - Wu CW, Chi CW, Ho CK, et al. Effect of arginase on splenic killer cell activity in patients with gastric cancer. Dig Dis Sci. 1994; 39(5): 1107–1112. - Proenza A, Oliver J, Palou A, et al. Breast and lung cancer are associated with a decrease in blood cell amino acid content. The Journal of Nutritional Biochemistry. 2003; 14(3): 133–138. - Mohan RR, Challa A, Gupta S, et al. Overexpression of Ornithine Decarboxylase in Prostate Cancer and Prostatic Fluid in Humans, Clinical Cancer Research. Clin Cancer Res. 1999; 5(1): 143–147. - Deng W, Jiang X, Mei Yu, et al. Role of ornithine decarboxylase in breast cancer. Acta Biochim Biophys Sin (Shanghai). 2008; 40(3): 235–243. - Yoshida M, Hayashi H, Taira M, et al. Elevated expression of the ornithine decarboxylase gene in human esophageal cancer . Cancer Res. 1992; 52(23): 6671–6675. - Satriano J, Matsufuji S, Murakami Y, et al. Agmatine suppresses proliferation by frameshift induction of antizyme and attenuation of cellular polyamine levels. J Biol Chem. 1998; 273(25): 15313–15316. - Regunathan S, Youngson C, Raasch W, et al. Imidazoline receptors and agmatine in blood vessels: a novel system inhibiting vascular smooth muscle proliferation . Pharmacol Exp Ther. 1996; 276(3): 1272–1282. - Xavier P, Belo L, Beires J, et al. Serum levels of VEGF and TNF-alpha and their association with C-reactive protein in patients with endometriosis. Arch Gynecol Obstet. 2006; 273(4): 227–231. - Vodolazkaia A, Yesilyurt BT, Kyama CM, et al. Vascular endothelial growth factor pathway in endometriosis: genetic variants and plasma biomarkers. Fertil Steril. 2016; 105(4): 988–996. - Yu-Hsien Lin K, Yin-Yi Chang C, Lin WC, et al. Increased risk of endometriosis in patients with endometritis- a nationwide cohort study involving 84,150 individuals. Ginekol Pol. 2020; 91(4): 193–200.