Carboxy terminus of heat shock protein (HSP) 70-interacting protein (CHIP) inhibits HSP70 in the heart
Abstract
Heat shock protein (HSP) 70 plays a critical role in protecting the heart from various stressor-induced cell injuries; the mechanism remains to be further understood. The present study aims to elucidate the effect of a probiotics-derived protein, LGG-derived protein p75 (LGP), in alleviating the ischemia/reperfusion (I/R)-induced heart injury. We treated rats with the I/R with or without preadministration with LGP. The levels of HSP70 and carboxy terminus of HSP70-interacting protein (CHIP) in the heart tissue were assessed by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The effect of CHIP on suppression of HSP70 and the effect of LGP on suppression of CHIP were investigated with an I/R rat model and a cell culture model. The results showed that I/R-induced infarction in the heart could be alleviated by pretreatment with LGP. HSP70 was detected in naïve rat heart tissue extracts. I/R treatment significantly suppressed the level of HSP70 and increased the levels of CHIP in the heart. A complex of CHIP/HSP70 was detected in heart tissue extracts. The addition of recombinant CHIP to culture inhibited HSP70 in heart cells. LGP was bound CHIP in heart cells and prevented the CHIP from binding HSP70. In summary, I/R can suppress HSP70 and increase CHIP in heart cells. CHIP can suppress HSP70 that can be prevented by pretreatment with LGP. The results imply that CHIP may be a potential target in the prevention of I/R-induced heart cell injury.
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L. rhamnosus has been linked to weight reduction, prevention of ischemia-reperfusion injury, and attenuation of cardiac hypertrophy and post-infarction heart failure in rodents.
“It has also been linked to weight reduction, prevention of ischemia-reperfusion injury, and attenuation of cardiac hypertrophy and post-infarction heart failure in rodents[403,418,419]”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [419]
Cites
Free radicals and antioxidants in normal physiological functions and human disease
Valko, M., Leibfritz, D., Moncol, J., Cronin, M. T. D., Mazur, M., & Telser, J. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2006.07.001 · Cited by 14,269 · see citing works
Hsp70 chaperones: Cellular functions and molecular mechanism
Mayer, M. P., & Bukau, B. (2005) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-004-4464-6 · Cited by 2,857 · see citing works
The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins
Connell, P. M., Ballinger, C. A., Jiang, J., Wu, Y., Thompson, L. J., Höhfeld, J., & Patterson, C. (2000) · Nature Cell Biology · doi:10.1038/35050618 · Cited by 1,002 · see citing works
Fishbein, M. C., Meerbaum, S., Y-Rit, J., Lando, U., Kanmatsuse, K., Mercier, J. C., Corday, E., & Ganz, W. (1981) · American Heart Journal · doi:10.1016/0002-8703(81)90226-x · Cited by 932 · see citing works
Yan, F., Cao, H., Cover, T. L., Whitehead, R. H., Washington, M. K., & Polk, D. B. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.11.022 · Cited by 828 · see citing works
Pathogenesis of Myocardial Ischemia-Reperfusion Injury and Rationale for Therapy
Turer, A. T., & Hill, J. A. (2010) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2010.03.032 · Cited by 635 · see citing works
Zhang, M., Windheim, M., Roe, S. M., Peggie, M. W., Cohen, P., Prodromou, C., & Pearl, L. H. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.09.023 · Cited by 420 · see citing works
Tien, M.-T., Girardin, S. E., Regnault, B., Bourhis, L. L., Dillies, M., Coppée, J., Bourdet‐Sicard, R., Sansonetti, P. J., & Pédron, T. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.2.1228 · Cited by 323 · see citing works
Wang, Y., Kirpich, I., Liu, Y., Ma, Z., Barve, S. S., McClain, C. J., & Feng, W. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2011.08.039 · Cited by 255 · see citing works
Martarelli, D., Verdenelli, M. C., Scuri, S., Cocchioni, M., Silvi, S., Cecchini, C., & Pompei, P. (2011) · Current Microbiology · doi:10.1007/s00284-011-9915-3 · Cited by 209 · see citing works
Pratt, W. B., Morishima, Y., Peng, H., & Osawa, Y. (2010) · Experimental Biology and Medicine · doi:10.1258/ebm.2009.009250 · Cited by 201 · see citing works
Identification of Residues on Hsp70 and Hsp90 Ubiquitinated by the Cochaperone CHIP
Kundrat, L., & Regan, L. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.11.017 · Cited by 106 · see citing works
Calpain-mediated Hsp70.1 cleavage in hippocampal CA1 neuronal death
Sahara, S., & Yamashima, T. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.02.087 · Cited by 104 · see citing works
Sharma, S., Singh, R. L., & Kakkar, P. (2010) · Food and Chemical Toxicology · doi:10.1016/j.fct.2010.11.041 · Cited by 94 · see citing works
Xing, H., Li, L., Xu, K., Shen, T. H., Chen, Y., Sheng, J., Chen, Y., Fu, S., Chen, C., Wang, J., et al. (2006) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2006.04306.x · Cited by 88 · see citing works
Brown, M. A., McGuinness, M., Wright, T., Ren, X., Wang, Y., Boivin, G. P., Hahn, H. S., Feldman, A. M., & Jones, W. K. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00170.2004 · Cited by 86 · see citing works
Stress for maintaining memory: HSP70 as a mobile messenger for innate and adaptive immunity
Chen, T., & Cao, X. (2010) · European Journal of Immunology · doi:10.1002/eji.201040616 · Cited by 76 · see citing works
TNF-α is required for late ischemic preconditioning but not for remote preconditioning of trauma
Ren, X., Wang, Y., & Jones, W. K. (2004) · Journal of Surgical Research · doi:10.1016/j.jss.2004.03.010 · Cited by 67 · see citing works
Protein kinase inhibitors can suppress stress-induced dissociation of Hsp27
Kato, K., Ito, H., Iwamoto, I., Iida, K., & Inaguma, Y. (2001) · Cell Stress and Chaperones · doi:10.1379/1466-1268(2001)006 · Cited by 51 · see citing works
Myocardial function improved by electromagnetic field induction of stress protein hsp70
George, I., Geddis, M. S., Lill, Z., Lin, H., Gomez, T., Blank, M., Oz, M. C., & Goodman, R. (2008) · Journal of Cellular Physiology · doi:10.1002/jcp.21461 · Cited by 44 · see citing works
Current Medical Treatments of Dyspepsia and Irritable Bowel Syndrome
Camilleri, M., & Tack, J. F. (2010) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2010.08.005 · Cited by 44 · see citing works
Reilly, N., Poylin, V. Y., Menconi, M. J., Onderdonk, A. B., Bengmark, S., & Hasselgren, P. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00770.2006 · Cited by 40 · see citing works
Protective role of heat shock protein 27 in gastric mucosal injury
Ebert, M. P., Schäfer, C., Chen, J., Hoffmann, J., Gu, P., Kubisch, C. H., Carl‐McGrath, S., Treiber, G., Malfertheiner, P., & Röcken, C. (2005) · The Journal of Pathology · doi:10.1002/path.1815 · Cited by 36 · see citing works
Matsuzaki, S., Szweda, P. A., Szweda, L. I., & Humphries, K. M. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.05.008 · Cited by 35 · see citing works
Meng, X., Banerjee, A. M., Ao, L., Meldrum, D. R., Cain, B. S., Shames, B. D., & Harken, A. H. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb09226.x · Cited by 29 · see citing works
Torigoe, Y., Takahashi, N., Hara, M., Yoshimatsu, H., & Saikawa, T. (2008) · Endocrinology · doi:10.1210/en.2008-1052 · Cited by 14 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Thirty Years of Lactobacillus rhamnosus GG
Capurso, L. (2019) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0000000000001170 · Cited by 385 · see citing works
Koch, C. D., Gladwin, M. T., Freeman, B. A., Lundberg, J. O., Weitzberg, E., & Morris, A. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.12.015 · Cited by 186 · see citing works
The influence of the human microbiome and probiotics on cardiovascular health
Ettinger, G., MacDonald, K., Reid, G., & Burton, J. P. (2014) · Gut Microbes · doi:10.4161/19490976.2014.983775 · Cited by 180 · see citing works
Qu, B., Jia, Y., Liu, Y., Wang, H., Ren, G., & Wang, H. (2015) · Cell Stress and Chaperones · doi:10.1007/s12192-015-0618-8 · Cited by 110 · see citing works
“2002) and that HSP70 binds to human aorta smooth muscle cell TLR-4, which up-regulates the activator protein-1 (AP-1)-dependent transcriptional activity of the TGF-β1 promoter (Zhao et al. 2012).”
BackgroundThe role of ubiquitin ligases in cardiac disease
Willis, M. S., Bevilacqua, A., Pulinilkunnil, T., Kienesberger, P. C., Tannu, M., & Patterson, C. (2013) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2013.11.008 · Cited by 89 · see citing works
Joshi, V., Amanullah, A., Upadhyay, A., Mishra, R., Kumar, A., & Mishra, A. (2016) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2016.00093 · Cited by 74 · see citing works
“The mouse model of ischemia/reperfusion-induced heart injury also suggested that CHIP suppresses Hsp70 in the heart (Zhao et al., 2012).”
BackgroundSadeghzadeh, J., Vakili, A., Sameni, H. R., Shadnoush, M., Bandegi, A., & Khorasani, M. Z. (2017) · Iranian Biomedical Journal · doi:10.18869/acadpub.ibj.21.3.174 · Cited by 42 · see citing works
Santos-Junior, V. D. A., Lollo, P. C. B., Cantero, M. A., Moura, C. S., Amaya‐Farfán, J., & Morato, P. N. (2018) · Brazilian Journal of Cardiovascular Surgery · doi:10.21470/1678-9741-2017-0169 · Cited by 27 · see citing works
Zhao, Y., Zhai, Q., Liu, H., Xi, X., Chen, D., & Liu, D. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.625105 · Cited by 24 · see citing works
Wu, J., Chen, S., Liu, Y., Liu, Z., Wang, D., & Cheng, Y. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105162 · Cited by 22 · see citing works
Tang, S., Lv, Y., Chen, H., Adam, A., Cheng, Y., Hartung, J., & Bao, E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086937 · Cited by 17 · see citing works
“associated with heart vascular disease [12,46].”
Zhang, X., Wu, J., Sha, J., Yang, B., Sun, J., & Bao, E. (2020) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2020.4560 · Cited by 17 · see citing works
“cardiomyocytes are engaged continuously in generating the powerful contractile force to pump blood to the whole body, and heat stress can lead to a surge in metabolic demand, followed by functional and structural disruption of these cells, resulting in heart failure (31,32).”
BackgroundEttinger, G., Burton, J. P., Gloor, G. B., & Reid, G. (2017) · PLoS ONE · doi:10.1371/journal.pone.0168622 · Cited by 12 · see citing works
CHIP-dependent regulation of the actin cytoskeleton is linked to neuronal cell membrane integrity
Dias, C., Nita, E., Faktor, J., Tynan, A. C., Hernychová, L., Vojtěšek, B., Nylandsted, J., Hupp, T. R., Kunath, T., & Ball, K. L. (2020) · iScience · doi:10.1016/j.isci.2021.102878 · Cited by 7 · see citing works
“CHIP, such as the insulin receptor (INSR) that link directly to organismal health (Adachi et al., 2007; Al-Ramahi et al., 2006; Morishima et al., 2008; Ronnebaum et al., 2013; Tawo et al., 2017; Zhao et al., 2012).”
BackgroundDong, J., Ma, Q., Yang, R., Zhang, X., Hua, Y., Ji, P., Yao, W., Yuan, Z., & Wei, Y. (2025) · Antioxidants · doi:10.3390/antiox14091140 · Cited by 5 · see citing works
“…vitro and in vivo HS models, we identified that HS specifically down-regulates Stub1 expression in cardiomyocytes-a phenomenon distinct from classical ischemia/hypoxia injury models [61], suggesting that different stress stimuli may disrupt myocardial homeostasis through unique molecular pathways.”
Pan, B., Kong, F., Ju, X., Song, J., Wang, L., Niu, Q. L., & Lu, X. (2023) · Toxicology · doi:10.1016/j.tox.2023.153610 · Cited by 5 · see citing works
Gacasan, C. A., Naudin, C. R., Weinberg, J., Askew, L. C., Barbian, M. E., Jones, D. P., & Jones, R. M. (2026) · Gut Microbes · doi:10.1080/19490976.2025.2609426 · Cited by 3 · see citing works
“7-12 These findings underscore the potential of microbiome-based therapies to improve vascular health and metabolic homeostasis.”
Dias, C., Nita, E., Faktor, J., Hernychová, L., Vojtěšek, B., Nylandsted, J., Hupp, T. R., Kunath, T., & Ball, K. L. (2020) · SSRN Electronic Journal · doi:10.2139/ssrn.3751766
Ettinger, G. (2014) · Scholarship@Western (Western University)
- Authors
- Zhao, B., Sun, G., Feng, G., Duan, W., Zhu, X., Chen, S., Hou, L., Jin, Z., & Yi, D.
- Affiliations
- Xijing Hospital (CN)
- Xian Central Hospital (CN)
- Corresponding author
- Jin, Zhenxiao
- Venue
- Journal of Physiology and Biochemistry
- Published
- 2012-03-29
- Volume
- 68
- Issue
- 4
- Pages
- 485-491
- ISSN
- 1138-7548 (ISSN-L)
- 1877-8755
- OpenAlex
- W2122291185
- Cited by
- 19
- References
- 26
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 1
- FWCI
- 0.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Physiology and Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- HSP70, CHIP, probiotics, myocardial ischemia-reperfusion injury, cardiac injury, cardioprotection, myocardial infarction
- MeSH terms
- Animals, Bacterial Proteins, Cardiotonic Agents, Cell Line, Male, Protein Binding, Myocardial Reperfusion Injury, Rats, Sprague-Dawley, HSP70 Heat-Shock Proteins, Myocytes, Cardiac, Ubiquitin-Protein Ligases, Rats, Proteolysis
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