Peri/epicellular protein disulfide isomerase-A1 acts as an upstream organizer of cytoskeletal mechanoadaptation in vascular smooth muscle cells
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Citações na Scopus
16
Tipo de produção
article
Data de publicação
2019
Título da Revista
ISSN da Revista
Título do Volume
Editora
AMER PHYSIOLOGICAL SOC
Autores
I, Andres Rodriguez
FERRAZ, Mariana S.
PELEGATI, Vitor B.
SANTOS, Aline M. dos
CESAR, Carlos L.
ALENCAR, Adriano M.
Citação
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, v.316, n.3, p.H566-H579, 2019
Resumo
Although redox processes closely interplay with mechanoresponses to control vascular remodeling, redox pathways coupling mechanostimulation to cellular cytoskeletal organization remain unclear. The peri/epicellular pool of protein disulfide isomerase-A1 (pecPDIA1) supports postinjury vessel remodeling. Using distinct models, we investigated whether pecPDIA1 could work as a redox-dependent organizer of cytoskeletal mechanoresponses. In vascular smooth muscle cells (VSMCs), pecPDIA1 immunoneutralization impaired stress fiber assembly in response to equibiaxial stretch and, under uniaxial stretch, significantly perturbed cell repositioning perpendicularly to stretch orientation. During cyclic stretch, pecPDIA1 supported thiol oxidation of the known mechanosensor beta(1)-integrin and promoted polarized compartmentalization of suifenylated proteins. Using traction force microscopy, we showed that pecPDIA1 organizes intracellular force distribution. The net contractile moment ratio of platelet-derived growth factor-exposed to basal VSMCs decreased from 0.90 +/- 0.09 (IgG-exposed controls) to 0.70 +/- 0.08 after pecPDIA1 neutralization (P < 0.05), together with an enhanced coefficient of variation for distribution of force modules, suggesting increased noise. Moreover, in a single cell model, pecPDIA1 neutralization impaired migration persistence without affecting total distance or velocity, whereas siRNA-mediated total PDIA1 silencing disabled all such variables of VSMC migration. Neither expression nor total activity of the master mechanotransmitter/regulator RhoA was affected by pecPDIA1 neutralization. However, cyclic stretch-induced focal distribution of membrane-bound RhoA was disrupted by pecPDI inhibition, which promoted a nonpolarized pattern of RhoA/caveolin-3 cluster colocalization. Accordingly, FRET biosensors showed that pecPDIA1 supports localized RhoA activity at cell protrusions versus perinuclear regions. Thus. pecPDI acts as a thiol redox-dependent organizer and noise reducer mechanism of cytoskeletal repositioning, oxidant generation, and localized RhoA activation during a variety of VSMC mechanoresponses. NEW & NOTEWORTHY Effects of a peri/epicellular pool of protein disulfide isomerase-A1 (pecPDIA1) during mechanoregulation in vascular smooth muscle cells (VSMCs) were highlighted using approaches such as equibiaxial and uniaxial stretch, random single cell migration, and traction force microscopy. pecPDIA1 regulates organization of the cytoskeleton and minimizes the noise of cell alignment, migration directionality, and persistence. pecPDIA1 mechanisms involve redox control of beta(1)-integrin and localized RhoA activation. pecPDIA1 acts as a novel organizer of mechanoadaptation responses in VSMCs.
Palavras-chave
cytoskeleton, mechanobiology, protein disulfide isomerase, redox, vascular smooth muscle cells
Referências
- Araujo TLS, 2017, FREE RADICAL BIO MED, V103, P199, DOI 10.1016/j.freeradbiomed.2016.12.021
- Benham AM, 2012, ANTIOXID REDOX SIGN, V16, P781, DOI 10.1089/ars.2011.4439
- Burgess A, 2010, P NATL ACAD SCI USA, V107, P12564, DOI 10.1073/pnas.0914191107
- Butler JP, 2002, AM J PHYSIOL-CELL PH, V282, pC595, DOI 10.1152/ajpcell.00270.2001
- Cameron JM, 2015, CURR BIOL, V25, P1520, DOI 10.1016/j.cub.2015.04.020
- Crescente M, 2016, ARTERIOSCL THROM VAS, V36, P1164, DOI 10.1161/ATVBAHA.116.307461
- Dajnowiec D, 2007, CLIN SCI, V113, P15, DOI 10.1042/CS200602337
- Damughatla AR, 2015, J MAGN RESON IMAGING, V41, P44, DOI 10.1002/jmri.24506
- Datla SR, 2014, AM J PHYSIOL-HEART C, V307, pH945, DOI 10.1152/ajpheart.00918.2013
- DOBRIN PB, 1978, PHYSIOL REV, V58, P397
- Dovas A, 2005, BIOCHEM J, V390, P1, DOI 10.1042/BJ20050104
- Eble JA, 2014, ANTIOXID REDOX SIGN, V20, P1977, DOI 10.1089/ars.2013.5294
- Fernandes DC, 2007, AM J PHYSIOL-CELL PH, V292, pC413, DOI 10.1152/ajpcell.00188.2006
- Fernandes DC, 2009, ARCH BIOCHEM BIOPHYS, V484, P197, DOI 10.1016/j.abb.2009.01.022
- Flaumenhaft R, 2016, BLOOD, V128, P893, DOI 10.1182/blood-2016-04-636456
- Goldyn AM, 2009, J CELL SCI, V122, P3644, DOI 10.1242/jcs.054866
- Hahn C, 2009, NAT REV MOL CELL BIO, V10, P53, DOI 10.1038/nrm2596
- Janiszewski M, 2005, J BIOL CHEM, V280, P40813, DOI 10.1074/jbc.M509255200
- Kawamura S, 2003, J BIOL CHEM, V278, P31111, DOI 10.1074/jbc.M300725200
- Krishnan R, 2011, AM J PHYSIOL-CELL PH, V300, pC146, DOI 10.1152/ajpcell.00195.2010
- Lahav J, 2002, BLOOD, V100, P2472, DOI 10.1182/blood-2002-12-0339
- Laurindo FRM, 2012, FREE RADICAL BIO MED, V52, P1954, DOI 10.1016/j.freeradbiomed.2012.02.037
- Montenegro MF, 2015, FREE RADICAL BIO MED, V85, P288, DOI 10.1016/j.freeradbiomed.2015.05.011
- Moretti AIS, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-16947-5
- Ochoa CD, 2008, AM J RESP CELL MOL, V39, P105, DOI 10.1165/rcmb.2007-0283OC
- Peixoto AS, 2018, J BIOL CHEM, V293, P1450, DOI 10.1074/jbc.M117.807016
- Pereira MBM, 2015, NAT COMMUN, V6, DOI 10.1038/ncomms7508
- Pereira MBM, 2014, NAT COMMUN, V5, DOI 10.1038/ncomms6159
- Pertz O, 2006, NATURE, V440, P1069, DOI 10.1038/nature04665
- Pescatore LA, 2012, J BIOL CHEM, V287, P29290, DOI 10.1074/jbc.M112.394551
- Rodriguez AI, 2015, ARTERIOSCL THROM VAS, V35, P430, DOI 10.1161/ATVBAHA.114.304936
- Sadok A, 2009, MOL CELL BIOL, V29, P3915, DOI 10.1128/MCB.01199-08
- Sathyanesan A, 2012, J NEUROSCI METH, V206, P165, DOI 10.1016/j.jneumeth.2012.02.019
- Schad JF, 2011, VASC CELL, V3, DOI 10.1186/2045-824X-3-21
- Moretti AIS, 2017, ARCH BIOCHEM BIOPHYS, V617, P106, DOI 10.1016/j.abb.2016.11.007
- Tanaka LY, 2017, FREE RADICAL BIO MED, V109, P11, DOI 10.1016/j.freeradbiomed.2017.01.025
- Tanaka LY, 2016, HYPERTENSION, V67, P613, DOI 10.1161/HYPERTENSIONAHA.115.06177
- Wang C, 2012, J BIOL CHEM, V287, P1139, DOI 10.1074/jbc.M111.303149
- Zhang WW, 2012, J BIOL CHEM, V287, P33996, DOI 10.1074/jbc.M112.369603