Share This Article:

Hyperglycemia Induced Changes in Vascular AKT3 May Inhibit Pressure-Induced Apoptosis in the Rat Inferior Venae Cavae

Abstract Full-Text HTML XML Download Download as PDF (Size:2028KB) PP. 41-50
DOI: 10.4236/ojemd.2015.54006    2,886 Downloads   3,249 Views   Citations

ABSTRACT

Background: Vein graft failure after bypass surgery is greatly increase in patients with diabetes mellitus. The cellular mechanisms underlying the cause of this failure are largely unexplored. Protein kinase B/AKT is a mechanically sensitive regulator of cellular growth and apoptosis. Herein we examine whether diabetes affects the regulation of AKT in response to increased venous loading. Methods: Inferior venae cavae (IVC) from the non-diabetic lean (LNZ) and the diabetic obese syndrome X Zucker(OSXZ) rats were isolated and incubated ex vivo under basal or pressurized conditions (120 mmHg). Protein expression, basal activation and the ability of increased pressure to activate AKT3 and apoptosis-related signaling were evaluated by immunoblot analysis. Results: Compared to that seen in the non-diabetic lean animals, increased venous pressure in the OSXZ rats was not characterized by increases in APAF-1 concentration, XIAP proteolysis, AIF cleavage, or Bad phosphorylation. This evidence of decreased apoptotic signaling was associated with increased basal p-AKT3 levels (+136% ± 13% P < 0.05 higher in the OSXZ vs. LNZ IVC). Conclusion: These data suggest that diabetes-associated increases in p-AKT3 may alter the ability of the IVC to undergo pressure induced apoptosis-related signaling. Further investigation is required to determine whether these changes are associated with the increased vein graft attrition seen in the diabetic population.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Rice, K. , Arvapalli, R. and Blough, E. (2015) Hyperglycemia Induced Changes in Vascular AKT3 May Inhibit Pressure-Induced Apoptosis in the Rat Inferior Venae Cavae. Open Journal of Endocrine and Metabolic Diseases, 5, 41-50. doi: 10.4236/ojemd.2015.54006.

References

[1] Hambly, R.I., Sherman, L., Mehta, J. and Aintablian, A. (1976) Reappraisal of the Role of the Diabetic State in Coronary Artery Disease. Chest, 70, 251-257. http://dx.doi.org/10.1378/chest.70.2.251
[2] Waller, B.F., Palumbo, P.J., Lie, J.T. and Roberts, W.C. (1980) Status of the Coronary Arteries at Necropsy in Diabetes Mellitus with Onset after Age 30 Years. Analysis of 229 Diabetic Patients with and without Clinical Evidence of Coronary Heart Disease and Comparison to 183 Control Subjects. The American Journal of Medicine, 69,498-506. http://dx.doi.org/10.1016/S0149-2918(05)80002-5
[3] Woodfield, S.L., Lundergan, C.F., Reiner, J.S., Greenhouse, S.W., Thompson, M.A., Rohrbeck, S.C., Deychak, Y., Simoons, M.L., Califf, R.M., Topol, E.J., et al. (1996) Angiographic Findings and Outcome in Diabetic Patients Treated with Thrombolytic Therapy for Acute Myocardial Infarction: The GUSTO-I Experience. Journal of the American College of Cardiology, 28, 1661-1669. http://dx.doi.org/10.1016/S0735-1097(96)00397-X
[4] (2000) Correction: The Effect of Previous Coronary-Artery Bypass Surgery on the Prognosis of Patients with Diabetes Who Have Acute Myocardial Infarction. The New England Journal of Medicine, 343, 980. http://dx.doi.org/10.1056/NEJM200009283431320
[5] Detre, K.M., Lombardero, M.S., Brooks, M.M., Hardison, R.M., Holubkov, R., Sopko, G., Frye, R.L. and Chaitman, B.R. (2000) The Effect of Previous Coronary-Artery Bypass Surgery on the Prognosis of Patients with Diabetes Who Have Acute Myocardial Infarction. Bypass Angioplasty Revascularization Investigation Investigators. The New England Journal of Medicine, 342, 989-997. http://dx.doi.org/10.1056/NEJM200004063421401
[6] The BARI Investigators (1997) Influence of Diabetes on 5-Year Mortality and Morbidity in a Randomized Trial Comparing CABG and PTCA in Patients with Multivessel Disease: The Bypass Angioplasty Revascularization Investigation (BARI). Circulation, 96, 1761-1769.
[7] Mompeo, B., Popov, D., Sima, A., Constantinescu, E. and Simionescu, M. (1998) Diabetes-Induced Structural Changes of Venous and Arterial Endothelium and Smooth Muscle Cells. Journal of Submicroscopic Cytology and Pathology, 30, 475-484.
[8] Rice, K.M., Desai, D.H., Kakarla, S.K., Katta, A., Preston, D.L., Wehner, P. and Blough, E.R. (2006) Diabetes Alters Vascular Mechanotransduction: Pressure-Induced Regulation of Mitogen Activated Protein Kinases in the Rat Inferior Vena Cava. Cardiovascular Diabetology, 5, 18. http://dx.doi.org/10.1186/1475-2840-5-18
[9] Pei-Ling Chiu, A., Wang, F.L., Lal, N., Wang, Y., Zhang, D.H., Hussein, B., Wan, A. Vlodavsky, I. and Rodrigues, B. (2014) Endothelial Cells Respond to Hyperglycemia by Increasing the LPL Transporter GPIHBP1. American Journal of Physiology—Endocrinology and Metabolism, 306, E1274-E1283. http://dx.doi.org/10.1152/ajpendo.00007.2014
[10] Martelli, A.M., Tabellini, G., Bressanin, D., Ognibene, A., Goto, K., Cocco, L. and Evangelisti, C. (2012) The Emerging Multiple Roles of Nuclear AKT. Biochimica et Biophysica Acta (BBA)—Molecular Cell Research, 1823, 2168-2178.http://dx.doi.org/10.1016/j.bbamcr.2012.08.017
[11] Buitenhuis, M. (2011) The Role of PI3K/Protein Kinase B (PKB/c-AKT) in Migration and Homing of Hematopoietic Stem and Progenitor Cells. Current Opinion in Hematology, 18, 226-230. http://dx.doi.org/10.1097/MOH.0b013e32834760e5
[12] Zhou, H.Y. and Huang, S.L. (2011) Role of mTOR Signaling in Tumor Cell Motility, Invasion and Metastasis. Current Protein & Peptide Science, 12, 30-42. http://dx.doi.org/10.2174/138920311795659407
[13] Pillai, V.B., Sundaresan, N.R. and Gupta, M.P. (2014) Regulation of AKT Signaling by Sirtuins: Its Implication in Cardiac Hypertrophy and Aging. Circulation Research, 114, 368-378. http://dx.doi.org/10.1161/CIRCRESAHA.113.300536
[14] Krepinsky, J.C., Li, Y., Chang, Y., Liu, L., Peng, F., Wu, D., Tang, D., Scholey, J. and Ingram, A.J. (2005) AKT Mediates Mechanical Strain-Induced Collagen Production by Mesangial Cells. Journal of the American Society of Nephrology, 16, 1661-1672. http://dx.doi.org/10.1681/ASN.2004100897
[15] Walker, K.S., Deak, M., Paterson, A., Hudson, K., Cohen, P. and Alessi, D.R. (1998) Activation of Protein Kinase B Beta and Gamma Isoforms by Insulin in Vivo and by 3-Phosphoinositide-Dependent Protein Kinase-1 in Vitro: Comparison with Protein Kinase B Alpha. Biochemical Journal, 331, 299-308.
[16] Tuttle, R.L., Gill, N.S., Pugh, W., Lee, J.P., Koeberlein, B., Furth, E.E., Polonsky, K.S., Naji, A. and Birnbaum, M.J. (2001) Regulation of Pancreatic Beta-Cell Growth and Survival by the Serine/Threonine Protein Kinase AKT1/PKBα. Nature Medicine, 7, 1133-1137. http://dx.doi.org/10.1038/nm1001-1133
[17] Chen, W.S., Peng, X.D., Wang, Y., Xu, P.Z., Chen, M.L., Luo, Y., Jeon, S.M., Coleman, K., Haschek, W.M., Bass, J., et al. (2009) Leptin Deficiency and Beta-Cell Dysfunction Underlie Type 2 Diabetes in Compound AKT Knockout Mice. Molecular and Cellular Biology, 29, 3151-3162. http://dx.doi.org/10.1128/MCB.01792-08
[18] O’Neill, B.T. and Abel, E.D. (2005) AKT1 in the Cardiovascular System: Friend or Foe? Journal of Clinical Investigation, 115, 2059-2064. http://dx.doi.org/10.1172/JCI25900
[19] Ding, L., Biswas, S., Morton, R.E., Smith, J.D., Hay, N., Byzova, T.V., Febbraio, M. and Podrez, E.A. (2012) AKT3 Deficiency in Macrophages Promotes Foam Cell Formation and Atherosclerosis in Mice. Cell Metabolism, 15, 861-872. http://dx.doi.org/10.1016/j.cmet.2012.04.020
[20] Corum, D.G., Tsichlis, P.N. and Muise-Helmericks, R.C. (2014) AKT3 Controls Mitochondrial Biogenesis and Autophagy via Regulation of the Major Nuclear Export Protein CRM-1. The FASEB Journal, 28, 395-407. http://dx.doi.org/10.1096/fj.13-235382
[21] Wright, G.L., Maroulakou, I.G., Eldridge, J., Liby, T.L., Sridharan, V., Tsichlis, P.N. and Muise-Helmericks, R.C. (2008) VEGF Stimulation of Mitochondrial Biogenesis: Requirement of AKT3 Kinase. The FASEB Journal, 22, 3264-3275. http://dx.doi.org/10.1096/fj.08-106468
[22] Nishio, K., Fukui, T., Tsunoda, F., Kawamura, K., Itoh, S., Konno, N., Ozawa, K. and Katagiri, T. (2005) Insulin Resistance as a Predictor for Restenosis after Coronary Stenting. International Journal of Cardiology, 103, 128-134. http://dx.doi.org/10.1016/j.ijcard.2004.08.039
[23] Easton, R.M., Cho, H., Roovers, K., Shineman, D.W., Mizrahi, M., Forman, M.S., Lee, V.M., Szabolcs, M., de Jong, R., Oltersdorf, T., et al. (2005) Role for AKT3/Protein Kinase Bγ in Attainment of Normal Brain Size. Molecular and Cellular Biology, 25, 1869-1878. http://dx.doi.org/10.1128/MCB.25.5.1869-1878.2005
[24] Shao, Y. and Aplin, A.E. (2010) AKT3-Mediated Resistance to Apoptosis in B-RAF-Targeted Melanoma Cells. Cancer Research, 70, 6670-6681. http://dx.doi.org/10.1158/0008-5472.CAN-09-4471
[25] Kirkegaard, T., Witton, C.J., Edwards, J., Nielsen, K.V., Jensen, L.B., Campbell, F.M., Cooke, T.G. and Bartlett, J.M. (2010) Molecular Alterations in AKT1, AKT2 and AKT3 Detected in Breast and Prostatic Cancer by FISH. Histopathology, 56, 203-211. http://dx.doi.org/10.1111/j.1365-2559.2009.03467.x
[26] Gagnon, V., Van Themsche, C., Turner, S., Leblanc, V. and Asselin, E. (2008) AKT and XIAP Regulate the Sensitivity of Human Uterine Cancer Cells to Cisplatin, Doxorubicin and Taxol. Apoptosis, 13, 259-271. http://dx.doi.org/10.1007/s10495-007-0165-6
[27] Novosyadlyy, R., Lann, D.E., Vijayakumar, A., Rowzee, A., Lazzarino, D.A., Fierz, Y., Carboni, J.M., Gottardis, M.M., Pennisi, P.A., Molinolo, A.A., et al. (2010) Insulin-Mediated Acceleration of Breast Cancer Development and Progression in a Nonobese Model of Type 2 Diabetes. Cancer Research, 70, 741-751. http://dx.doi.org/10.1158/0008-5472.CAN-09-2141
[28] Ferguson, R.D., Novosyadlyy, R., Fierz, Y., Alikhani, N., Sun, H., Yakar, S. and Leroith, D. (2012) Hyperinsulinemia Enhances c-Myc-Mediated Mammary Tumor Development and Advances Metastatic Progression to the Lung in a Mouse Model of Type 2 Diabetes. Breast Cancer Research, 14, R8. http://dx.doi.org/10.1186/bcr3089
[29] Ferguson, R.D., Gallagher, E.J., Cohen, D., Tobin-Hess, A., Alikhani, N., Novosyadlyy, R., Haddad, N., Yakar, S. and LeRoith, D. (2013) Hyperinsulinemia Promotes Metastasis to the Lung in a Mouse Model of Her2-Mediated Breast Cancer. Endocrine-Related Cancer, 20, 391-401. http://dx.doi.org/10.1530/ERC-12-0333
[30] Hakkak, R., Korourian, S. and Melnyk, S. (2013) Obesity, Oxidative Stress and Breast Cancer Risk. Journal of Cancer Science and Therapy, 5, e129.
[31] Fieber, C.B., Eldridge, J., Taha, T.A., Obeid, L.M. and Muise-Helmericks, R.C. (2006) Modulation of Total AKT Kinase by Increased Expression of a Single Isoform: Requirement of the Sphingosine-1-Phosphate Receptor, Edg3/S1P3, for the VEGF-Dependent Expression of AKT3 in Primary Endothelial Cells. Experimental Cell Research, 312, 1164-1173. http://dx.doi.org/10.1016/j.yexcr.2006.01.022
[32] Santi, S.A. and Lee, H. (2010) The AKT Isoforms Are Present at Distinct Subcellular Locations. AJP: Cell Physiology, 298, C580-C591. http://dx.doi.org/10.1152/ajpcell.00375.2009
[33] Buroker, N.E., Ning, X.H., Zhou, Z.N., Li, K., Cen, W.J., Wu, X.F., Zhu, W.Z., Scott, C.R. and Chen, S.H. (2012) AKT3, ANGPTL4, eNOS3, and VEGFA Associations with High Altitude Sickness in Han and Tibetan Chinese at the Qinghai-Tibetan Plateau. International Journal of Hematology, 96, 200-213. http://dx.doi.org/10.1007/s12185-012-1117-7
[34] Liu, X., Kim, C.N., Yang, J., Jemmerson, R. and Wang, X. (1996) Induction of Apoptotic Program in Cell-Free Extracts: Requirement for dATP and Cytochrome c. Cell, 86, 147-157. http://dx.doi.org/10.1016/S0092-8674(00)80085-9
[35] Norberg, E., Karlsson, M., Korenovska, O., Szydlowski, S., Silberberg, G., Uhlen, P., Orrenius, S. and Zhivotovsky, B. (2010) Critical Role for Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 in the AIF-Mediated Apoptosis. The EMBO Journal, 29, 3869-3878. http://dx.doi.org/10.1038/emboj.2010.253
[36] Polster, B.M., Basanez, G., Etxebarria, A., Hardwick, J.M. and Nicholls, D.G. (2005) Calpain I Induces Cleavage and Release of Apoptosis-Inducing Factor from Isolated Mitochondria. Journal of Biological Chemistry, 280, 6447-6454. http://dx.doi.org/10.1074/jbc.M413269200
[37] Deveraux, Q.L. and Reed, J.C. (1999) IAP Family Proteins—Suppressors of Apoptosis. Genes & Development, 13, 239-252. http://dx.doi.org/10.1101/gad.13.3.239

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.