PMID- 31518570
OWN - NLM
STAT- MEDLINE
DCOM- 20200803
LR  - 20200904
IS  - 1095-8584 (Electronic)
IS  - 0022-2828 (Linking)
VI  - 136
DP  - 2019 Nov
TI  - Carbonic anhydrase II/sodium-proton exchanger 1 metabolon complex in 
      cardiomyopathy of ob(-/-) type 2 diabetic mice.
PG  - 53-63
LID - S0022-2828(18)31255-0 [pii]
LID - 10.1016/j.yjmcc.2019.09.005 [doi]
AB  - Heart failure is the leading cause of death among diabetic people. Cellular and 
      molecular entities leading to diabetic cardiomyopathy are, however, poorly 
      understood. Coupling of cardiac carbonic anhydrase II (CAII) and Na(+)/H(+) 
      exchanger 1 (NHE1) to form a transport metabolon was analyzed in obese type 2 
      diabetic mice (ob(-/-)) and control heterozygous littermates (ob(+/-)). 
      Echocardiography showed elevated systolic interventricular septum thickness and 
      systolic posterior wall thickness in ob(-/-) mice at 9 and 16 weeks. ob(-/-) mice 
      showed increased left ventricular (LV) weight/tibia length ratio and increased 
      cardiomyocyte cross sectional area as compared to controls, indicating cardiac 
      hypertrophy. Immunoblot analysis showed increased CAII expression in LV samples 
      of ob(-/-)vs. ob(+/-) mice, and augmented Ser(703) phosphorylation on NHE1 in 
      ob(-/-) hearts. Reciprocal co-immunoprecipitation analysis showed strong 
      association of CAII and NHE1 in LV samples of ob(-/-) mice. NHE1-dependent rate 
      of intracellular pH (pH(i)) normalization after transient acid loading of 
      isolated cardiomyocytes was higher in ob(-/-) mice vs. ob(+/-). NHE transport 
      activity was also augmented in cultured H9C2 rat cardiomyoblasts treated with 
      high glucose/high palmitate, and it was normalized after CA inhibition. We 
      conclude that the NHE1/CAII metabolon complex is exacerbated in diabetic 
      cardiomyopathy of ob(-/-) mice, which may lead to perturbation of pH(i) and 
      [Na(+)] and [Ca(2+)] handling in these diseased hearts.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Jaquenod De Giusti, Carolina
AU  - Jaquenod De Giusti C
AD  - Centro de Investigaciones Cardiovasculares CIC-CONICET, Facultad de Ciencias 
      Medicas, Universidad Nacional de La Plata, Calle 60 y 120, 1900 La Plata, 
      Argentina; Established Investigators of CONICET, Argentina.
FAU - Blanco, Paula G
AU  - Blanco PG
AD  - Servicio de Cardiologia, Facultad de Ciencias Veterinarias, UNLP, Argentina; 
      Established Investigators of CONICET, Argentina.
FAU - Lamas, Paula A
AU  - Lamas PA
AD  - Centro de Investigaciones Cardiovasculares CIC-CONICET, Facultad de Ciencias 
      Medicas, Universidad Nacional de La Plata, Calle 60 y 120, 1900 La Plata, 
      Argentina.
FAU - Carrizo Velasquez, Fernanda
AU  - Carrizo Velasquez F
AD  - Centro de Investigaciones Cardiovasculares CIC-CONICET, Facultad de Ciencias 
      Medicas, Universidad Nacional de La Plata, Calle 60 y 120, 1900 La Plata, 
      Argentina.
FAU - Lofeudo, Juan M
AU  - Lofeudo JM
AD  - Centro de Investigaciones Cardiovasculares CIC-CONICET, Facultad de Ciencias 
      Medicas, Universidad Nacional de La Plata, Calle 60 y 120, 1900 La Plata, 
      Argentina.
FAU - Portiansky, Enrique L
AU  - Portiansky EL
AD  - Laboratorio de Analisis de Imagenes, Facultad de Ciencias Veterinarias, UNLP, 
      Argentina; Established Investigators of CONICET, Argentina.
FAU - Alvarez, Bernardo V
AU  - Alvarez BV
AD  - Centro de Investigaciones Cardiovasculares CIC-CONICET, Facultad de Ciencias 
      Medicas, Universidad Nacional de La Plata, Calle 60 y 120, 1900 La Plata, 
      Argentina; Established Investigators of CONICET, Argentina. Electronic address: 
      balvarez@med.unlp.edu.ar.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190910
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Carbonic Anhydrase Inhibitors)
RN  - 0 (Slc9a1 protein, mouse)
RN  - 0 (Slc9a1 protein, rat)
RN  - 0 (Sodium-Hydrogen Exchanger 1)
RN  - 452VLY9402 (Serine)
RN  - EC 4.2.1.- (Carbonic Anhydrase II)
RN  - Z52H4811WX (Ethoxzolamide)
SB  - IM
MH  - Animals
MH  - Carbonic Anhydrase II/antagonists & inhibitors/*metabolism
MH  - Carbonic Anhydrase Inhibitors/pharmacology
MH  - Cardiomegaly/diagnostic imaging/metabolism/*pathology
MH  - Diabetes Mellitus, Experimental/complications/pathology
MH  - Diabetes Mellitus, Type 2/*complications/metabolism/pathology
MH  - Electrocardiography
MH  - Ethoxzolamide/pharmacology
MH  - Female
MH  - Heart Ventricles/pathology
MH  - Hydrogen-Ion Concentration
MH  - Mice, Mutant Strains
MH  - Mice, Transgenic
MH  - Myocytes, Cardiac/metabolism/pathology
MH  - Phosphorylation
MH  - Protein Processing, Post-Translational
MH  - Rats
MH  - Serine/metabolism
MH  - Sodium-Hydrogen Exchanger 1/*metabolism
OTO - NOTNLM
OT  - Carbonic anhydrase II
OT  - Diabetic cardiomyopathy
OT  - Intracellular pH
OT  - NHE1
EDAT- 2019/09/14 06:00
MHDA- 2020/08/04 06:00
CRDT- 2019/09/14 06:00
PHST- 2018/12/04 00:00 [received]
PHST- 2019/07/17 00:00 [revised]
PHST- 2019/09/14 06:00 [pubmed]
PHST- 2020/08/04 06:00 [medline]
PHST- 2019/09/14 06:00 [entrez]
AID - S0022-2828(18)31255-0 [pii]
AID - 10.1016/j.yjmcc.2019.09.005 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2019 Nov;136:53-63. doi: 10.1016/j.yjmcc.2019.09.005. Epub 
      2019 Sep 10.