PMID- 36995910
OWN - NLM
STAT- MEDLINE
DCOM- 20230515
LR  - 20240502
IS  - 1522-1601 (Electronic)
IS  - 8750-7587 (Print)
IS  - 0161-7567 (Linking)
VI  - 134
IP  - 5
DP  - 2023 May 1
TI  - STIM1 ablation impairs exercise-induced physiological cardiac hypertrophy and 
      dysregulates autophagy in mouse hearts.
PG  - 1287-1299
LID - 10.1152/japplphysiol.00363.2022 [doi]
AB  - Cardiac stromal interaction molecule 1 (STIM1), a key mediator of store-operated 
      Ca(2+) entry (SOCE), is a known determinant of cardiomyocyte pathological growth 
      in hypertrophic cardiomyopathy. We examined the role of STIM1 and SOCE in 
      response to exercise-dependent physiological hypertrophy. Wild-type (WT) mice 
      subjected to exercise training (WT-Ex) showed a significant increase in exercise 
      capacity and heart weight compared with sedentary (WT-Sed) mice. Moreover, 
      myocytes from WT-Ex hearts displayed an increase in length, but not width, 
      compared with WT-Sed myocytes. Conversely, exercised cardiac-specific STIM1 
      knock-out mice (cSTIM1KO-Ex), although displaying significant increase in heart 
      weight and cardiac dilation, evidenced no changes in myocyte size and displayed a 
      decreased exercise capacity, impaired cardiac function, and premature death 
      compared with sedentary cardiac-specific STIM1 knock-out mice (cSTIM1KO-Sed). 
      Confocal Ca(2+) imaging demonstrated enhanced SOCE in WT-Ex myocytes compared 
      with WT-Sed myocytes with no measurable SOCE detected in cSTIM1KO myocytes. 
      Exercise training induced a significant increase in cardiac phospho-Akt Ser473 in 
      WT mice but not in cSTIM1KO mice. No differences were observed in phosphorylation 
      of mammalian target of rapamycin (mTOR) and glycogen synthase kinase (GSK) in 
      exercised versus sedentary cSTIM1KO mice hearts. cSTIM1KO-Sed mice showed 
      increased basal MAPK phosphorylation compared with WT-Sed that was not altered by 
      exercise training. Finally, histological analysis revealed exercise resulted in 
      increased autophagy in cSTIM1KO but not in WT myocytes. Taken together, our 
      results suggest that adaptive cardiac hypertrophy in response to exercise 
      training involves STIM1-mediated SOCE. Our results demonstrate that STIM1 is 
      involved in and essential for the myocyte longitudinal growth and mTOR activation 
      in response to endurance exercise training.NEW & NOTEWORTHY Store-operated Ca(2+) 
      entry (SOCE) has been implicated in pathological cardiac hypertrophy; however, 
      its role in physiological hypertrophy is unknown. Here we report that SOCE is 
      also essential for physiological cardiac hypertrophy and functional adaptations 
      in response to endurance exercise. These adaptations were associated with 
      activation of AKT/mTOR pathway and curtailed cardiac autophagy and degeneration. 
      Thus, SOCE is a common mechanism and an important bifurcation point for signaling 
      paths involved in physiological and pathological hypertrophy.
FAU - Bonilla, Ingrid M
AU  - Bonilla IM
AUID- ORCID: 0000-0003-1435-3870
AD  - Department of Physiology and Cell Biology, College of Medicine, The Ohio State 
      University, Columbus, Ohio, United States.
AD  - Veterans Affairs Caribbean Healthcare System, San Juan, Puerto Rico, United 
      States.
AD  - Department of Pharmacology and Toxicology, School of Medicine, University of 
      Puerto Rico, San Juan, Puerto Rico, United States.
FAU - Baine, Stephen
AU  - Baine S
AD  - Department of Pharmacology, College of Pharmacy, The Ohio State University, 
      Columbus, Ohio, United States.
FAU - Pokrass, Anastasia
AU  - Pokrass A
AD  - Department of Physiology and Cell Biology, College of Medicine, The Ohio State 
      University, Columbus, Ohio, United States.
FAU - Mariangelo, Juan Ignacio Elio
AU  - Mariangelo JIE
AD  - Department of Physiology and Cell Biology, College of Medicine, The Ohio State 
      University, Columbus, Ohio, United States.
FAU - Kalyanasundaram, Anuradha
AU  - Kalyanasundaram A
AD  - Department of Physiology and Cell Biology, College of Medicine, The Ohio State 
      University, Columbus, Ohio, United States.
AD  - Bob and Corrine Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis 
      Heart & Lung Research Institute, Columbus, Ohio, United States.
FAU - Bogdanov, Vladimir
AU  - Bogdanov V
AD  - Department of Physiology and Cell Biology, College of Medicine, The Ohio State 
      University, Columbus, Ohio, United States.
FAU - Mezache, Louisa
AU  - Mezache L
AD  - Department of Biomedical Engineering, College of Engineering, The Ohio State 
      University, Columbus, Ohio, United States.
FAU - Sakuta, Galina
AU  - Sakuta G
AD  - Department of Physiology and Cell Biology, College of Medicine, The Ohio State 
      University, Columbus, Ohio, United States.
FAU - Beard, Casey M
AU  - Beard CM
AD  - Department of Physiology and Cell Biology, College of Medicine, The Ohio State 
      University, Columbus, Ohio, United States.
FAU - Belevych, Andriy
AU  - Belevych A
AD  - Department of Physiology and Cell Biology, College of Medicine, The Ohio State 
      University, Columbus, Ohio, United States.
FAU - Tikunova, Svetlana
AU  - Tikunova S
AUID- ORCID: 0000-0002-2101-9996
AD  - Department of Physiology and Cell Biology, College of Medicine, The Ohio State 
      University, Columbus, Ohio, United States.
FAU - Terentyeva, Radmila
AU  - Terentyeva R
AD  - Department of Physiology and Cell Biology, College of Medicine, The Ohio State 
      University, Columbus, Ohio, United States.
FAU - Terentyev, Dmitry
AU  - Terentyev D
AUID- ORCID: 0000-0002-9530-7384
AD  - Department of Physiology and Cell Biology, College of Medicine, The Ohio State 
      University, Columbus, Ohio, United States.
FAU - Davis, Jonathan
AU  - Davis J
AD  - Department of Physiology and Cell Biology, College of Medicine, The Ohio State 
      University, Columbus, Ohio, United States.
FAU - Veeraraghavan, Rengasayee
AU  - Veeraraghavan R
AD  - Department of Biomedical Engineering, College of Engineering, The Ohio State 
      University, Columbus, Ohio, United States.
FAU - Carnes, Cynthia A
AU  - Carnes CA
AD  - Department of Pharmacology, College of Pharmacy, The Ohio State University, 
      Columbus, Ohio, United States.
FAU - Gyorke, Sandor
AU  - Gyorke S
AUID- ORCID: 0000-0002-0821-1983
AD  - Department of Physiology and Cell Biology, College of Medicine, The Ohio State 
      University, Columbus, Ohio, United States.
LA  - eng
GR  - R01 HL063043/HL/NHLBI NIH HHS/United States
GR  - R01 HL074045/HL/NHLBI NIH HHS/United States
GR  - R01 HL142588/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230330
PL  - United States
TA  - J Appl Physiol (1985)
JT  - Journal of applied physiology (Bethesda, Md. : 1985)
JID - 8502536
RN  - 0 (Calcium Channels)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 0 (Stromal Interaction Molecule 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - SY7Q814VUP (Calcium)
RN  - 0 (Stim1 protein, mouse)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Myocytes, Cardiac/metabolism
MH  - *Calcium Channels/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Stromal Interaction Molecule 1/metabolism
MH  - Cardiomegaly/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Mice, Knockout
MH  - Calcium/metabolism
MH  - Calcium Signaling
MH  - Mammals/metabolism
PMC - PMC10190841
OTO - NOTNLM
OT  - SOCE
OT  - STIM1
OT  - calcium
OT  - cardiac hypertrophy
OT  - exercise
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2023/03/31 06:00
MHDA- 2023/05/15 06:42
PMCR- 2024/05/01
CRDT- 2023/03/30 12:23
PHST- 2023/05/15 06:42 [medline]
PHST- 2023/03/31 06:00 [pubmed]
PHST- 2023/03/30 12:23 [entrez]
PHST- 2024/05/01 00:00 [pmc-release]
AID - JAPPL-00363-2022 [pii]
AID - 10.1152/japplphysiol.00363.2022 [doi]
PST - ppublish
SO  - J Appl Physiol (1985). 2023 May 1;134(5):1287-1299. doi: 
      10.1152/japplphysiol.00363.2022. Epub 2023 Mar 30.