Leiomyoma phosphoproteins involved in inhibition of oxidative stress and synthesis of reactive oxygen species

Ura,Blendi; Monasta,Lorenzo; Arrigoni,Giorgio; Licastro,Danilo; Di Lorenzo,Giovanni; Romano,Federico; Gaita,Bartolomea; Scrimin,Federica; Ricci,Giuseppe

doi:10.3892/ijmm.2019.4377

Leiomyoma phosphoproteins involved in inhibition of oxidative stress and synthesis of reactive oxygen species

Authors:
- Blendi Ura
- Lorenzo Monasta
- Giorgio Arrigoni
- Danilo Licastro
- Giovanni Di Lorenzo
- Federico Romano
- Bartolomea Gaita
- Federica Scrimin
- Giuseppe Ricci
View Affiliations

Affiliations: Institute for Maternal and Child Health‑IRCCS ‘Burlo Garofolo’, I‑34137 Trieste, Italy, Department of Biomedical Sciences, University of Padova, I‑35121 Padova, Italy, Centro di Biomedicina Molecolare, Area Science Park, I‑34149 Trieste, Italy
Published online on: October 21, 2019 https://doi.org/10.3892/ijmm.2019.4377
Pages: 2329-2335

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Uterine leiomyomas are benign smooth muscle cell tumors originating from the myometrium. The present study focused on leiomyoma and myometrium phosphoproteome enrichment by using immobilized metal affinity chromatography (IMAC). The phosphoproteome was analyzed by two‑dimensional gel electrophoresis coupled with mass spectrometry. Western blotting was used for data validation. The results from IMAC identified 26 proteins significantly differentially phosphorylated in leiomyomas compared with normal myometrium. Three upregulated proteins (peroxiredoxin 2, protein disulfide isomerase family A member 3 and peroxiredoxin 4) were further validated by western blotting. Ingenuity pathway analysis revealed that four phosphoproteins were involved in the inhibition of oxidative stress and synthesis of reactive oxygen species. The present results demonstated for the first time an association between oxidative stress and phosphorylation in leiomyoma development.

View Figures

View References

1	Ura B, Scrimin F, Arrigoni G, Aloisio M, Monasta L and Ricci G: Dysregulated chaperones associated with cell proliferation and negative apoptosis regulation in the uterine leiomyoma. Oncol Lett. 15:8005–8010. 2018.PubMed/NCBI
2	Okolo S: Incidence, aetiology and epidemiology of uterine fibroids. Best Pract Res Clin Obstet Gynaecol. 22:571–588. 2008. View Article : Google Scholar : PubMed/NCBI
3	Ura B, Di Lorenzo G, Romano F, Monasta L, Mirenda G, Scrimin F and Ricci G: Interstitial fluid in gynecologic tumors and its possible application in the clinical practice. Int J Mol Sci. 19:2018. View Article : Google Scholar : PubMed/NCBI
4	Moravek MB, Yin P, Ono M, Coon JS V, Dyson MT, Navarro A, Marsh EE, Chakravarti D, Kim JJ, Wei JJ and Bulun SE: Ovarian steroids, stem cells and uterine leiomyoma: Therapeutic implications. Hum Reprod Update. 21:1–12. 2015. View Article : Google Scholar
5	Ura B, Scrimin F, Monasta L, Radillo O and Ricci G: Association between up-regulated expression proteins and circulating steroidal hormones in leiomyoma. Med Hypotheses. 85:5152015. View Article : Google Scholar : PubMed/NCBI
6	Ardito F, Giuliani M, Perrone D, Troiano G and Lo Muzio L: The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review). Int J Mol Med. 40:271–280. 2017. View Article : Google Scholar : PubMed/NCBI
7	Nishi H, Shaytan A and Panchenko AR: Physicochemical mechanisms of protein regulation by phosphorylation. Front Genet. 5:2702014. View Article : Google Scholar : PubMed/NCBI
8	Ura B, Monasta L, Arrigoni G, Battisti I, Licastro D, Di Lorenzo G, Romano F, Aloisio M, Peterlunger I, Stabile G, et al: Phosphoproteins involved in the inhibition of apoptosis and in cell survival in the leiomyoma. J Clin Med. 8:2019. View Article : Google Scholar : PubMed/NCBI
9	Kovács KA, Oszter A, Göcze PM, Környei JL and Szabó I: Comparative analysis of cyclin D1 and oestrogen receptor (alpha and beta) levels in human leiomyoma and adjacent myometrium. Mol Hum Reprod. 7:1085–1091. 2001. View Article : Google Scholar : PubMed/NCBI
10	Yu L, Saile K, Swartz CD, He H, Zheng X, Kissling GE, Di X, Lucas S, Robboy SJ and Dixon D: Differential expression of receptor tyrosine kinases (RTKs) and IGF-I pathway activation in human uterine leiomyomas. Mol Med. 14:264–275. 2008. View Article : Google Scholar : PubMed/NCBI
11	Chegini N, Luo X, Ding L and Ripley D: The expression of Smads and transforming growth factor beta receptors in leiomyoma and myometrium and the effect of gonadotropin releasing hormone analogue therapy. Mol Cell Endocrinol. 209:9–16. 2003. View Article : Google Scholar : PubMed/NCBI
12	Fletcher NM, Abusamaan MS, Memaj I, Saed MG, Al-Hendy A, Diamond MP and Saed GM: Oxidative stress: A key regulator of leiomyoma cell survival. Fertil Steril. 107:1387.e1–1394.e1. 2017. View Article : Google Scholar
13	Fletcher NM, Saed MG, Abu-Soud HM, Al-Hendy A, Diamond MP and Saed GM: Uterine fibroids are character-ized by an impaired antioxidant cellular system: Potential role of hypoxia in the pathophysiology of uterine fibroids. J Assist Reprod Genet. 30:969–974. 2013. View Article : Google Scholar : PubMed/NCBI
14	Storz P: KRas, ROS and the initiation of pancreatic cancer. Small GTPases. 8:38–42. 2017. View Article : Google Scholar :
15	Storz P and Toker A: Protein kinase D mediates a stress-induced NF-kappaB activation and survival pathway. EMBO J. 22:109–120. 2003. View Article : Google Scholar :
16	Schroyer AL, Stimes NW, Abi Saab WF and Chadee DN: MLK3 phosphorylation by ERK1/2 is required for oxidative stress-induced invasion of colorectal cancer cells. Oncogene. 37:1031–1040. 2018. View Article : Google Scholar :
17	Carcoforo P, Ura B, Mischiati C, Squerzanti M, Lanzara V, Cervellati C, Calza R, De Laureto PP, Frare E, Portinari M, et al: Comparative proteomic analysis of ductal breast carcinoma demonstrates an altered expression of chaperonins and cytoskel-etal proteins. Mol Med Rep. 7:1700–1704. 2013. View Article : Google Scholar : PubMed/NCBI
18	Ura B, Monasta L, Arrigoni G, Franchin C, Radillo O, Peterlunger I, Ricci G and Scrimin F: A proteomic approach for the identification of biomarkers in endometrial cancer uterine aspirate. Oncotarget. 8:109536–109545. 2017. View Article : Google Scholar
19	Ura B, Scrimin F, Arrigoni G, Athanasakis E, Aloisio M, Monasta L and Ricci G: Abnormal expression of leiomyoma cytoskeletal proteins involved in cell migration. Oncol Rep. 35:3094–3100. 2016. View Article : Google Scholar : PubMed/NCBI
20	Ura B, Scrimin F, Franchin C, Arrigoni G, Licastro D, Monasta L and Ricci G: Identification of proteins with different abundance associated with cell migration and proliferation in leiomyoma interstitial fluid by proteomics. Oncol Lett. 13:3912–3920. 2017. View Article : Google Scholar : PubMed/NCBI
21	Lemmon MA and Schlessinger J: Cell signaling by receptor tyrosine kinases. Cell. 141:1117–1134. 2010. View Article : Google Scholar : PubMed/NCBI
22	Basu A, Banerjee H, Rojas H, Martinez SR, Roy S, Jia Z, Lilly MB, De León M and Casiano CA: Differential expression of peroxiredoxins in prostate cancer: Consistent upregulation of PRDX3 and PRDX4. Prostate. 71:755–765. 2011. View Article : Google Scholar :
23	Jiang H, Wu L, Mishra M, Chawsheen HA and Wei Q: Expression of peroxiredoxin 1 and 4 promotes human lung cancer malignancy. Am J Cancer Res. 4:445–460. 2014.PubMed/NCBI
24	Yi N, Xiao MB, Ni WK, Jiang F, Lu CH and Ni RZ: High expression of peroxiredoxin 4 affects the survival time of colorectal cancer patients, but is not an independent unfavorable prognostic factor. Mol Clin Oncol. 2:767–772. 2014. View Article : Google Scholar : PubMed/NCBI
25	Rogalla T, Ehrnsperger M, Preville X, Kotlyarov A, Lutsch G, Ducasse C, Paul C, Wieske M, Arrigo AP, Buchner J and Gaestel M: Regulation of Hsp27 oligomerization, chaperone function, and protective activity against oxidative stress/tumor necrosis factor alpha by phosphorylation. J Biol Chem. 274:18947–18956. 1999. View Article : Google Scholar : PubMed/NCBI
26	Garrido C, Brunet M, Didelot C, Zermati Y, Schmitt E and Kroemer G: Heat shock proteins 27 and 70: Anti-apoptotic proteins with tumorigenic properties. Cell Cycle. 5:2592–2601. 2006. View Article : Google Scholar : PubMed/NCBI
27	Kamariah N, Sek MF, Eisenhaber B, Eisenhaber F and Grüber G: Transition steps in peroxide reduction and a molecular switch for peroxide robustness of prokaryotic peroxiredoxins. Sci Rep. 6:376102016. View Article : Google Scholar : PubMed/NCBI
28	Kwon T, Rho JK, Lee JC, Park YH, Shin HJ, Cho S, Kang YK, Kim BY, Yoon DY and Yu DY: An important role for peroxiredoxin II in survival of A549 lung cancer cells resistant to gefitinib. Exp Mol Med. 47:e1652015. View Article : Google Scholar : PubMed/NCBI
29	Abdullah M, Schultz H, Kähler D, Branscheid D, Dalhoff K, Zabel P, Vollmer E and Goldmann T: Expression of the acute phase protein haptoglobin in human lung cancer and tumor-free lung tissues. Pathol Res Pract. 205:639–647. 2009. View Article : Google Scholar : PubMed/NCBI
30	Fedorovych IP, Tymochko MF, Fedevych IuM, Fetsich TG and Korobov VM: Serum haptoglobin in lung cancer patients. Ukr Biokhim Zh 1978. 67:103–105. 1995.In Ukrainian.