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Pflugers Arch. 2017 Dec;469(12):1603-1613. doi: 10.1007/s00424-017-2046-3. Epub 2017 Aug 5.

The naked mole-rat exhibits an unusual cardiac myofilament protein profile providing new insights into heart function of this naturally subterranean rodent.

Author information

1
Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
2
Sam and Ann Barshop Institute for Aging and Longevity Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
3
Department of Cell and Molecular Physiology, Health Sciences Division, Loyola University Chicago, Maywood, IL, USA.
4
Center for Genetic Medicine, Northwestern University, Chicago, IL, USA.
5
Heart, Lung and Vascular Institute, University of Cincinnati, Cincinnati, OH, USA.
6
Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
7
Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. rbuffen@calicolabs.com.
8
Sam and Ann Barshop Institute for Aging and Longevity Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. rbuffen@calicolabs.com.
9
Calico Life Sciences, 1170 Veterans Blvd, South San Francisco, CA, 94080, USA. rbuffen@calicolabs.com.

Abstract

The long-lived, hypoxic-tolerant naked mole-rat well-maintains cardiac function over its three-decade-long lifespan and exhibits many cardiac features atypical of similar-sized laboratory rodents. For example, they exhibit low heart rates and resting cardiac contractility, yet have a large cardiac reserve. These traits are considered ecophysiological adaptations to their dank subterranean atmosphere of low oxygen and high carbon dioxide levels and may also contribute to negligible declines in cardiac function during aging. We asked if naked mole-rats had a different myofilament protein signature to that of similar-sized mice that commonly show both high heart rates and high basal cardiac contractility. Adult mouse ventricles predominantly expressed α-myosin heavy chain (97.9 ± 0.4%). In contrast, and more in keeping with humans, β myosin heavy chain was the dominant isoform (79.0 ± 2.0%) in naked mole-rat ventricles. Naked mole-rat ventricles diverged from those of both humans and mice, as they expressed both cardiac and slow skeletal isoforms of troponin I. This myofilament protein profile is more commonly observed in mice in utero and during cardiomyopathies. There were no species differences in phosphorylation of cardiac myosin binding protein-C or troponin I. Phosphorylation of both ventricular myosin light chain 2 and cardiac troponin T in naked mole-rats was approximately half that observed in mice. Myofilament function was also compared between the two species using permeabilized cardiomyocytes. Together, these data suggest a cardiac myofilament protein signature that may contribute to the naked mole-rat's suite of adaptations to its natural subterranean habitat.

KEYWORDS:

Heart; Hypoxia; Naked mole-rat; Neoteny; Slow skeletal troponin I; β myosin heavy chain

PMID:
28780592
PMCID:
PMC5856255
DOI:
10.1007/s00424-017-2046-3
[Indexed for MEDLINE]
Free PMC Article

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