Gender-Dependent Alteration of Ca2+ and TNFα Signaling in db /db Mice, an Obesity-Linked Type 2 Diabetic Model

Frontiers in Physiology
Carmen DelgadoLaetitia Pereira

Abstract

Cardiovascular complications are the primary death cause in type 2 diabetes, where inflammation can play a role. We, and others, have previously shown that, in diabetic cardiomyopathy, cardiac dysfunction is associated with Ca2+ mishandling. It is possible that diabetic cardiomyopathy differently affects men and women, as the latter present higher risk to develop heart failure and a higher plasmatic level of the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFα), than men. However, the gender-dependent regulation of Ca2+ signaling in diabetes and its relationship with TNFα signaling are still unclear. Here, we analyzed TNFα signaling pathway and its role in Ca2+ signaling dysfunction in male and female rodent models of type 2 diabetes linked to obesity (db/db mice) using confocal microscopy in freshly isolated cardiomyocytes. TNFα increased [Ca2+]i transient amplitude and accelerated its decay without affecting SR Ca2+ load or Ca2+ spark frequency in cells from control mice. All TNFα effects on Ca2+ handling were prevented by the inhibition of the ceramidase and the phospholipase A2 (PLA2). While the plasmatic level of TNFα was similar in male and female db/db mice, only male db/db hearts over-expressed both TNFα con...Continue Reading

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Citations

Aug 25, 2020·British Journal of Pharmacology·José Alberto Navarro-GarcíaGema Ruiz-Hurtado
Mar 29, 2020·Frontiers in Physiology·Gaia FaveroRita Rezzani
May 23, 2021·Acta Physiologica·Almudena Val-BlascoMaria Fernández-Velasco

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Methods Mentioned

BETA
confocal microscopy
electrophoresis

Software Mentioned

GraphPad Prism
Quantity One

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