Login Register Cart 0
Generic placeholder image

Current HIV Research

Editor-in-Chief

ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Intrinsic Apoptotic Pathway Genes of Circulating Blood Neutrophils Triggered during HIV Infection and Remained Stimulated in ART Patients

Author(s): A K M Muraduzzaman, Nabeela Mahboob Islam, Shahina Tabassum and Saif Ullah Munshi*

Volume 21, Issue 2, 2023

Published on: 13 June, 2023

Page: [122 - 127] Pages: 6

DOI: 10.2174/1570162X21666230519164239

Price: $65

Abstract

Background: The intrinsic apoptotic pathway of neutrophils in Human Immunodeficiency Virus (HIV) infection results in spontaneous neutrophil death. There is a scarcity of data regarding the gene expression of an intrinsic apoptotic pathway of neutrophils in HIV patients.

Objective: The objective of this study was to observe the differential expression of some important genes involved in the intrinsic apoptotic pathway of HIV patients, including those who were receiving antiretroviral therapy (ART).

Methods: Blood samples were collected from asymptomatic, symptomatic, ART receiver HIV patients, and healthy individuals. Total RNA was extracted from neutrophils and subjected to quantitative real-time PCR assay. CD4+T cells and an automated complete blood count were performed.

Results: Among the asymptomatic, symptomatic, and ART receiver HIV patients (n=20 in each group), median CD4+T counts were 633, 98, and 565 cells/ml, and the length of HIV infection in months (± SD) was 24.06 ± 21.36, 62.05 ± 25.51, and 69.2 ± 39.67, respectively. Compared with healthy controls, intrinsic apoptotic pathway genes, i.e., BAX, BIM, Caspase-3, Caspase-9, MCL-1, and Calpain-1, were upregulated to 1.21 ± 0.33, 1.8 ± 0.25, 1.24 ± 0.46, 1.54 ± 0.21, 1.88 ± 0.30, and 5.85 ± 1.34 fold in the asymptomatic group, and even more significantly, i.e., 1.51 ± 0.43, 2.09 ± 1.13, 1.85 ± 1.22, 1.72 ± 0.85, 2.26 ± 1.34, and 7.88 ± 3.31 fold in symptomatic patients, respectively. Despite CD4+ T-cell levels increased in the ART receiver group, these genes did not approach the level of healthy or asymptomatic and remained significantly upregulated.

Conclusion: The genes involved in the intrinsic apoptotic pathway in circulating neutrophils during HIV infection were stimulated in vivo, and ART reduced the expression of those upregulated genes but did not return to the level of asymptomatic or healthy individuals.

Keywords: Neutrophil, apoptosis, HIV, calpain-1, MCL-1, ART.

« Previous Next »
Graphical Abstract

[1]
Roilides E, Mertins S, Eddy J, Walsh TJ, Pizzo PA, Rubin M. Impairment of neutrophil chemotactic and bactericidal function in children infected with human immunodeficiency virus type 1 and partial reversal after in vitro exposure to granulocyte-macrophage colony-stimulating factor. J Pediatr 1990; 117(4): 531-40.
[http://dx.doi.org/10.1016/S0022-3476(05)80684-5] [PMID: 2170609]
[2]
Elbim C, Prevot MH, Bouscarat F, et al. Polymorphonuclear neutrophils from human immunodeficiency virus- infected patients show enhanced activation, diminished fMLP-induced L- selectin shedding, and an impaired oxidative burst after cytokine priming. Blood 1994; 84(8): 2759-66.
[http://dx.doi.org/10.1182/blood.V84.8.2759.2759] [PMID: 7522641]
[3]
Salmen S, Terán G, Borges L, et al. Increased Fas-mediated apoptosis in polymorphonuclear cells from HIV-infected patients. Clin Exp Immunol 2004; 137(1): 166-72.
[http://dx.doi.org/10.1111/j.1365-2249.2004.02503.x] [PMID: 15196258]
[4]
Kuritzkes DR. Neutropenia, neutrophil dysfunction, and bacterial infection in patients with human immunodeficiency virus disease: The role of granulocyte colony-stimulating factor. Clin Infect Dis 2000; 30(2): 256-70.
[http://dx.doi.org/10.1086/313642] [PMID: 10671324]
[5]
Pitrak DL, Bak PM, DeMarais P, Novak RM, Andersen BR. Depressed neutrophil superoxide production in human immunodeficiency virus infection. J Infect Dis 1993; 167(6): 1406-10.
[http://dx.doi.org/10.1093/infdis/167.6.1406] [PMID: 8388903]
[6]
Salmen S, Montes H, Soyano A, Hernández D, Berrueta L. Mechanisms of neutrophil death in human immunodeficiency virus-infected patients: Role of reactive oxygen species, caspases and map kinase pathways. Clin Exp Immunol 2007; 150(3): 539-45.
[http://dx.doi.org/10.1111/j.1365-2249.2007.03524.x] [PMID: 17956581]
[7]
Maianski NA, Maianski AN, Kuijpers TW, Roos D. Apoptosis of neutrophils. Acta Haematol 2004; 111(1-2): 56-66.
[http://dx.doi.org/10.1159/000074486] [PMID: 14646345]
[8]
Westphal D, Dewson G, Czabotar PE, Kluck RM. Molecular biology of Bax and Bak activation and action. Biochim Biophys Acta Mol Cell Res 2011; 1813(4): 521-31.
[http://dx.doi.org/10.1016/j.bbamcr.2010.12.019] [PMID: 21195116]
[9]
Cowburn AS, Summers C, Dunmore BJ, et al. Granulocyte/macrophage colony-stimulating factor causes a paradoxical increase in the BH3-only pro-apoptotic protein Bim in human neutrophils. Am J Respir Cell Mol Biol 2011; 44(6): 879-87.
[http://dx.doi.org/10.1165/rcmb.2010-0101OC] [PMID: 20705940]
[10]
Knepper-Nicolai B, Savill J, Brown SB. Constitutive apoptosis in human neutrophils requires synergy between calpains and the proteasome downstream of caspases. J Biol Chem 1998; 273(46): 30530-6.
[http://dx.doi.org/10.1074/jbc.273.46.30530] [PMID: 9804822]
[11]
Akgul C, Moulding DA, Edwards SW. Molecular control of neutrophil apoptosis. FEBS Lett 2001; 487(3): 318-22.
[http://dx.doi.org/10.1016/S0014-5793(00)02324-3] [PMID: 11163351]
[12]
Moulding DA, Quayle JA, Hart CA, Edwards SW. Mcl-1 expression in human neutrophils: Regulation by cytokines and correlation with cell survival. Blood 1998; 92(7): 2495-502.
[http://dx.doi.org/10.1182/blood.V92.7.2495] [PMID: 9746790]
[13]
Moulding DA, Akgul C, Derouet M, White MRH, Edwards SW. BCL-2 family expression in human neutrophils during delayed and accelerated apoptosis. J Leukoc Biol 2001; 70(5): 783-92.
[http://dx.doi.org/10.1189/jlb.70.5.783] [PMID: 11698499]
[14]
Pongracz J, Webb P, Wang K, Deacon E, Lunn OJ, Lord JM. Spontaneous neutrophil apoptosis involves caspase 3-mediated activation of protein kinase C-delta. J Biol Chem 1999; 274(52): 37329-34.
[http://dx.doi.org/10.1074/jbc.274.52.37329] [PMID: 10601300]
[15]
Taneja R, Parodo J, Jia SH, Kapus A, Rotstein OD, Marshall JC. Delayed neutrophil apoptosis in sepsis is associated with maintenance of mitochondrial transmembrane potential and reduced caspase-9 activity. Crit Care Med 2004; 32(7): 1460-9.
[http://dx.doi.org/10.1097/01.CCM.0000129975.26905.77] [PMID: 15241089]
[16]
Heit B, Jones G, Knight D, et al. HIV and other lentiviral infections cause defects in neutrophil chemotaxis, recruitment, and cell structure: Immunorestorative effects of granulocyte-macrophage colony-stimulating factor. J Immunol 2006; 177(9): 6405-14.
[http://dx.doi.org/10.4049/jimmunol.177.9.6405] [PMID: 17056572]
[17]
Kim JS, Nam MH, An SSA, et al. Comparison of the automated fluorescence microscopic viability test with the conventional and flow cytometry methods. J Clin Lab Anal 2011; 25(2): 90-4.
[http://dx.doi.org/10.1002/jcla.20438] [PMID: 21437999]
[18]
Zhang S, Fantozzi I, Tigno DD, et al. Bone morphogenetic proteins induce apoptosis in human pulmonary vascular smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2003; 285(3): L740-54.
[http://dx.doi.org/10.1152/ajplung.00284.2002] [PMID: 12740218]
[19]
Yang GJ, Ko CN, Zhong HJ, Leung CH, Ma DL. Structure-based discovery of a selective KDM5A inhibitor that exhibits anti-cancer activity via inducing cell cycle arrest and senescence in breast cancer cell lines. Cancers 2019; 11(1): 92.
[http://dx.doi.org/10.3390/cancers11010092] [PMID: 30650517]
[20]
Thanuthanakhun N, Nuntakarn L, Sampattavanich S, et al. Investigation of FoxO3 dynamics during erythroblast development in β-thalassemia major. PLoS One 2017; 12(11): e0187610.
[http://dx.doi.org/10.1371/journal.pone.0187610] [PMID: 29099866]
[21]
Xu L, Xu Y, Jing Z, et al. Altered expression pattern of miR-29a, miR-29b and the target genes in myeloid leukemia. Exp Hematol Oncol 2014; 3(1): 17.
[http://dx.doi.org/10.1186/2162-3619-3-17] [PMID: 25006537]
[22]
Mendias CL, Schwartz AJ, Grekin JA, Gumucio JP, Sugg KB. Changes in muscle fiber contractility and extracellular matrix production during skeletal muscle hypertrophy. J Appl Physiol 2017; 122(3): 571-9.
[http://dx.doi.org/10.1152/japplphysiol.00719.2016]
[23]
Beena V, Ramnath V, Sreekumar KP, Karthiayini K, Philomina PT, Girija D. Crystal protein of a novel bacillus thuringiensis strain inducing cell cycle arrest and apoptotic cell death in human leukemic cells. Sci Rep 2019; 9(1): 9661.
[http://dx.doi.org/10.1038/s41598-019-45928-z] [PMID: 31273223]
[24]
Shimada H, Kogure N, Noro E, et al. High glucose stimulates expression of aldosterone synthase (CYP 11B2) and secretion of aldosterone in human adrenal cells. FEBS Open Bio 2017; 7(9): 1410-21.
[http://dx.doi.org/10.1002/2211-5463.12277] [PMID: 28904869]
[25]
Willis SN, Fletcher JI, Kaufmann T, et al. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 2007; 315(5813): 856-9.
[http://dx.doi.org/10.1126/science.1133289] [PMID: 17289999]
[26]
Lomonosova E, Chinnadurai G. BH3-only proteins in apoptosis and beyond: An overview. Oncogene 2008; 27(S1): S2-S19.
[http://dx.doi.org/10.1038/onc.2009.39]
[27]
Elbim C, Monceaux V, Mueller YM, et al. Early divergence in neutrophil apoptosis between pathogenic and nonpathogenic simian immunodeficiency virus infections of nonhuman primates. J Immunol 2008; 181(12): 8613-23.
[http://dx.doi.org/10.4049/jimmunol.181.12.8613] [PMID: 19050281]
[28]
Arnoult D, Petit F, Lelièvre JD, et al. Caspase-dependent and -independent T-cell death pathways in pathogenic simian immunodeficiency virus infection: Relationship to disease progression. Cell Death Differ 2003; 10(11): 1240-52.
[http://dx.doi.org/10.1038/sj.cdd.4401289] [PMID: 14576776]
[29]
Altznauer F, Conus S, Cavalli A, Folkers G, Simon HU. Calpain-1 regulates Bax and subsequent Smac-dependent caspase-3 activation in neutrophil apoptosis. J Biol Chem 2004; 279(7): 5947-57.
[http://dx.doi.org/10.1074/jbc.M308576200] [PMID: 14612448]
[30]
Gao G, Dou QP. N-terminal cleavage of Bax by calpain generates a potent proapoptotic 18-kDa fragment that promotes Bcl-2-independent cytochrome C release and apoptotic cell death. J Cell Biochem 2001; 80(1): 53-72.
[http://dx.doi.org/10.1002/1097-4644(20010101)80:1<53:AID-JCB60>3.0.CO;2-E] [PMID: 11029754]
[31]
Lichtner M, Mengoni F, Mastroianni CM, et al. HIV protease inhibitor therapy reverses neutrophil apoptosis in AIDS patients by direct calpain inhibition. Apoptosis 2006; 11(5): 781-7.
[http://dx.doi.org/10.1007/s10495-006-5699-5] [PMID: 16528469]
[32]
Aluja D, Delgado-Tomás S, Ruiz-Meana M, Barrabés JA, Inserte J. calpains as potential therapeutic targets for myocardial hypertrophy. Int J Mol Sci 2022; 23(8): 4103.
[http://dx.doi.org/10.3390/ijms23084103] [PMID: 35456920]
[33]
Zhang M, Wang G, Peng T. Calpain-mediated mitochondrial damage: An emerging mechanism contributing to cardiac disease. Cells 2021; 10(8): 2024.
[http://dx.doi.org/10.3390/cells10082024] [PMID: 34440793]
[34]
Fraietta JA, Mueller YM, Yang G, et al. Type I interferon upregulates Bak and contributes to T cell loss during human immunodeficiency virus (HIV) infection. PLoS Pathog 2013; 9(10): e1003658.
[http://dx.doi.org/10.1371/journal.ppat.1003658] [PMID: 24130482]
[35]
Bae J, Leo CP, Hsu SY, Hsueh AJW. MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, encodes a proapoptotic protein possessing only the BH3 domain. J Biol Chem 2000; 275(33): 25255-61.
[http://dx.doi.org/10.1074/jbc.M909826199] [PMID: 10837489]
[36]
Marriott HM, Bingle CD, Read RC, et al. Dynamic changes in Mcl-1 expression regulate macrophage viability or commitment to apoptosis during bacterial clearance. J Clin Invest 2005; 11c5(2): 359-68.
[http://dx.doi.org/10.1172/JCI200521766]
[37]
Catarzi S, Marcucci T, Papucci L, et al. Apoptosis and Bax, Bcl-2, Mcl-1 expression in neutrophils of Crohnʼs disease patients. Inflamm Bowel Dis 2008; 14(6): 819-25.
[http://dx.doi.org/10.1002/ibd.20397] [PMID: 18266233]

Rights & Permissions Print Cite
Article Metrics
21
2
© 2024 Bentham Science Publishers | Privacy Policy