Small heat shock protein 20 interacts with protein phosphatase-1 and enhances sarcoplasmic reticulum calcium cycling

Jiang Qian, Elizabeth Vafiadaki, Stela M. Florea, Vivek P. Singh, Weizhong Song, Chi Kung Lam, Yigang Wang, Qunying Yuan, Tracy J. Pritchard, Wenfeng Cai, Kobra Haghighi, Patricia Rodriguez, Hong Sheng Wang, Despina Sanoudou, Guo Chang Fan, Evangelia G. Kranias

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Background: Heat shock proteins (Hsp) are known to enhance cell survival under various stress conditions. In the heart, the small Hsp20 has emerged as a key mediator of protection against apoptosis, remodeling, and ischemia/reperfusion injury. Moreover, Hsp20 has been implicated in modulation of cardiac contractility ex vivo. The objective of this study was to determine the in vivo role of Hsp20 in the heart and the mechanisms underlying its regulatory effects in calcium (Ca) cycling. Methods and results: Hsp20 overexpression in intact animals resulted in significant enhancement of cardiac function, coupled with augmented Ca cycling and sarcoplasmic reticulum Ca load in isolated cardiomyocytes. This was associated with specific increases in phosphorylation of phospholamban (PLN) at both Ser16 and Thr17, relieving its inhibition of the apparent Ca affinity of SERCA2a. Accordingly, the inotropic effects of Hsp20 were abrogated in cardiomyocytes expressing nonphosphorylatable PLN (S16A/T17A). Interestingly, the activity of type 1 protein phosphatase (PP1), a known regulator of PLN signaling, was significantly reduced by Hsp20 overexpression, suggesting that the Hsp20 stimulatory effects are partially mediated through the PP1-PLN axis. This hypothesis was supported by cell fractionation, coimmunoprecipitation, and coimmunolocalization studies, which revealed an association between Hsp20, PP1, and PLN. Furthermore, recombinant protein studies confirmed a physical interaction between AA 73 to 160 in Hsp20 and AA 163 to 330 in PP1. Conclusions: Hsp20 is a novel regulator of sarcoplasmic reticulum Ca cycling by targeting the PP1-PLN axis. These findings, coupled with the well-recognized cardioprotective role of Hsp20, suggest a dual benefit of targeting Hsp20 in heart disease.

Original languageEnglish
Pages (from-to)1429-1438
Number of pages10
JournalCirculation Research
Volume108
Issue number12
DOIs
Publication statusPublished - 10 Jun 2011
Externally publishedYes

Fingerprint

HSP20 Heat-Shock Proteins
Small Heat-Shock Proteins
Protein Phosphatase 1
Sarcoplasmic Reticulum
Calcium
Cardiac Myocytes
Cell Fractionation
Heat-Shock Proteins
Reperfusion Injury
Recombinant Proteins
phospholamban
Heart Diseases
Cell Survival
Phosphorylation
Apoptosis

Keywords

  • contractility
  • phosphatase
  • phospholamban
  • sarcoplasmic reticulum

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Qian, J., Vafiadaki, E., Florea, S. M., Singh, V. P., Song, W., Lam, C. K., ... Kranias, E. G. (2011). Small heat shock protein 20 interacts with protein phosphatase-1 and enhances sarcoplasmic reticulum calcium cycling. Circulation Research, 108(12), 1429-1438. https://doi.org/10.1161/CIRCRESAHA.110.237644

Small heat shock protein 20 interacts with protein phosphatase-1 and enhances sarcoplasmic reticulum calcium cycling. / Qian, Jiang; Vafiadaki, Elizabeth; Florea, Stela M.; Singh, Vivek P.; Song, Weizhong; Lam, Chi Kung; Wang, Yigang; Yuan, Qunying; Pritchard, Tracy J.; Cai, Wenfeng; Haghighi, Kobra; Rodriguez, Patricia; Wang, Hong Sheng; Sanoudou, Despina; Fan, Guo Chang; Kranias, Evangelia G.

In: Circulation Research, Vol. 108, No. 12, 10.06.2011, p. 1429-1438.

Research output: Contribution to journalArticle

Qian, J, Vafiadaki, E, Florea, SM, Singh, VP, Song, W, Lam, CK, Wang, Y, Yuan, Q, Pritchard, TJ, Cai, W, Haghighi, K, Rodriguez, P, Wang, HS, Sanoudou, D, Fan, GC & Kranias, EG 2011, 'Small heat shock protein 20 interacts with protein phosphatase-1 and enhances sarcoplasmic reticulum calcium cycling', Circulation Research, vol. 108, no. 12, pp. 1429-1438. https://doi.org/10.1161/CIRCRESAHA.110.237644
Qian, Jiang ; Vafiadaki, Elizabeth ; Florea, Stela M. ; Singh, Vivek P. ; Song, Weizhong ; Lam, Chi Kung ; Wang, Yigang ; Yuan, Qunying ; Pritchard, Tracy J. ; Cai, Wenfeng ; Haghighi, Kobra ; Rodriguez, Patricia ; Wang, Hong Sheng ; Sanoudou, Despina ; Fan, Guo Chang ; Kranias, Evangelia G. / Small heat shock protein 20 interacts with protein phosphatase-1 and enhances sarcoplasmic reticulum calcium cycling. In: Circulation Research. 2011 ; Vol. 108, No. 12. pp. 1429-1438.
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AU - Song, Weizhong

AU - Lam, Chi Kung

AU - Wang, Yigang

AU - Yuan, Qunying

AU - Pritchard, Tracy J.

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AU - Haghighi, Kobra

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