Immunohistochemical examination of p97/VCP expression in developing mouse pancreas and liver

Year 2021, Volume: 4 Issue: 3, 334 - 339, 21.05.2021

Bahar Kartal , Ebru Alimoğulları , Gülben Akcan , Sevil Çaylı , Muaz Alperen Vergili

https://doi.org/10.32322/jhsm.904567

Abstract

Abstract
Aim: The 97-kDa Valosin-containing protein has important functions in proteolysis. Although the expression of p97 / VCP has been studied in many types of cells and tissues, the localization of p97 / VCP at cellular level in developing mouse pancreas and liver has not been determined. Therefore, the aim of our study was investigate the immuolocalization of p97/VCP in the rat fetal and postnatal liver and pancreas.
Material Methods: The liver and pancreas from fetal, postnatal (1, 5, 15, 35 days old ) and adult (50 days old) mice were examined by using immunohistochemistry in order to determine the expression of p97/VCP. Furthermore the development of mouse pancreas and liver were histomorphologically analyzed under light microscope.
Results: The histological structures of the mouse pancreas and liver were maintained in postnatal period. The histological differences between endocrine and exocrine pancreas were significantly observed from the postnatal 5th day. The expression of p97/VCP in Langerhans islets was determined from day 5. p97/VCP expression was also seen in the exocrine pancreas in all postnatal days. p97/VCP was expressed in developing pancreatic and liver tissues and its expression was increased with the development.
Conclusion: This study is the first to examine the distribution and the localization of p97/VCP in the fetal and postnatal rat liver and pancreas. This study forms the basis for clinical studies in order to determine the function of p97 / VCP in liver and pancreatic cells.

Keywords

p97/VCP, postnatal development, pancreas, liver

References

• Ye Y, Meyer HH, Rapoport TA. The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol.Nature 2001; 414: 652-6.
• Xue L, Blythe E, Freiberger E, Mamrosh  E, Hebert A, Reitsma J. Valosin-containing protein (VCP)–Adaptor Interactions are Exceptionally Dynamic and Subject to Differential Modulation by a VCP Inhibitor. Mol Cell Proteomics 2016; 15: 2970-86.
• Ciechanover A. Intracellular protein degradation from a vague idea through the lysosome and the ubiquitin-proteasome system and on to human diseases and drug targeting: Nobel Lecture, December 8, 2004. Ann N Y Acad Sci 2007; 1116: 1–28.
• Lord JM, Roberts LM, Stirling CJ. Quality control: another player joins the ERAD cast. Curr Biol 2005; 15: R963–R964.
• Cao K, Nakajima R, Meyer HH, Zheng Y. The AAA-ATPase Cdc48/p97 regulates spindle disassembly at the end of mitosis. Cell 2003; 115: 355-67.
• Voges D , Zwick P,  Baumeister W. The 26S proteasome: a molecular machine designed for controlled proteolysis. Annu Rev Biochem 1999; 68: 1015-68.
• Song C, Wang O, Li H. ATPase Activity of p97-Valosin-containing Protein (VCP). J Biol Chem 2002; 278: 3648–55.
• Maurizi M, Li C. AAA proteins: in search of a common molecular basis. EMBO Rep 2001; 2: 980–5.
• Wang Y, Shirogane T, Liu D, Harper W, Elledge L. Exit from exit: resetting the cell cycle through Amn1 inhibition of G protein signaling. Cell 2003; 112: 697-709.
• Kondo H, Rabouille C, Newman R, et al. p47 is a cofactor for p97-mediated membrane fusion. Nature 1997; 388: 75-8.
• Dai RM, Li CC. Valosin-containing protein is a multi-ubiquitin chaintargeting factor required in ubiquitin-proteasome degradation. Nat Cell Biol 2001; 3: 740-4.
• Meusser B, Hirsch C, Jarosch E, Sommer T. ERAD: the long road to destruction. Nat Cell Biol 2005; 7: 766-72.
• Klein JB, Barati MT, Wu R, et al. Akt-mediated valosin-containing protein 97 phosphorylation regulates its association with ubiquitinated proteins. J Biol Chem 2005; 280: 31870-81.
• Cayli S, Klug J, Chapiro J, et al. The COP9 signalosome interacts ATP-dependently with p97/VCP and controls the ubiquitination status of proteins bound to p97/VCP. J Biol Chem 2009; 284: 34944-953.
• Ozsoy A, Cayli S, Sahin C, Ocakli S, Sanci T, İlhan D. Altered expression of p97/Valosin containing protein and impaired autophagy in preeclamptic human placenta. Placenta 2018; 67: 45-53
• Cayli S, Erdemir F, Ocaklı S. Interaction between smad1 and p97/vcp in rat testis and epididymis during the postnatal development. Reprod Sci 2012; 19: 190–201.
• Cayli S, Ocakli S, Erdemi F, et al. Developmental expression of p97/VCP (Valosincontaining protein) and Jab1/CSN5 in the rat testis and epididymis. Reprod Biol Endocrinol 2011; 9: 117.
• Ortak H, Cayli S, Tas U, Ocakli S, Söğüt E, Demir HD. Expression of p97/VCP and ubiquitin during postnatal development of the degenerating rat retina. J Mol Hist 2012; 43: 17–25.
• Donna H, David K, Peter W. p97: An emerging target for cancer, neurodegenerative diseases, and viral infections. J Med Chem 2020; 12: 1892-907.
• Anelya A, Margarita R, Elena F, Alexey K, Olga D, Kseniya D. VCP expression decrease as a biomarker of preclinical and early clinical stages of Parkinson’s disease. Sci Rep 2020; 10: 827.
• Hongyang S, Yizhong P, Weijian H, Ning Z, Dao W. Emerging role of VCP/p97 in cardiovascular diseases: novel insights and therapeutic opportunities. Biochem Soc Trans 2021; 49: 485-94.
• Lan B , Chai S , Wang P , Wang K . VCP/p97/Cdc48, A linking of protein homeostasis and cancer therapy. Curr Mol Med 2017; 17: 608-18.
• Nakkas H, Gumuskaya Ocal B, Kipel S, et al. Ubiquitin proteasome system and autophagy associated proteins in human testicular tumors. Tissue Cell 2021; 71: 101513.