Loss of function of transcription factor EB remodels lipid metabolism and cell death pathways in the cardiomyocyte.

Glucolipotoxicity following nutrient overload causes cardiomyocyte injury by inhibiting TFEB and suppressing lysosomal function. We ascertained whether in addition to the amount, the type of fatty acids (FAs) and duration of FA exposure regulate TFEB action and dictate cardiomyocyte viability. Saturated FA, palmitate, but not polyunsaturated FAs decreased TFEB content in a concentration- and time-dependent manner in cardiomyocytes.

Lysosomal Biology and Function: Modern View of Cellular Debris Bin.

Lysosomes are the main proteolytic compartments of mammalian cells comprising of a battery of hydrolases. Lysosomes dispose and recycle extracellular or intracellular macromolecules by fusing with endosomes or autophagosomes through specific waste clearance processes such as chaperone-mediated autophagy or microautophagy. The proteolytic end product is transported out of lysosomes via transporters or vesicular membrane trafficking.

Lysophosphatidic acid receptor mRNA levels in heart and white adipose tissue are associated with obesity in mice and humans.

Background: Lysophosphatidic acid (LPA) receptor signaling has been implicated in cardiovascular and obesity-related metabolic disease. However, the distribution and regulation of LPA receptors in the myocardium and adipose tissue remain unclear.

Objectives: This study aimed to characterize the mRNA expression of LPA receptors (LPA1-6) in the murine and human myocardium and adipose tissue, and its regulation in response to obesity.

Autophagic dysregulation in doxorubicin cardiomyopathy.

Doxorubicin (DOX)-induced cardiotoxicity has been a well-known phenomenon to clinicians and scientists for decades; however, molecular mechanisms underlying DOX cardiotoxicity are still being uncovered. Although the majority of prior research have implicated nuclear and mitochondrial events to be an important etiological aspects of DOX cardiomyopathy, recent discoveries in autophagy have highlighted the renewed interest in the role of lysosome in DOX cardiomyopathy. Indeed, dysregulation of lysosomal autophagy is observed in pre-clinical models of DOX cardiotoxicity.

Doxorubicin impairs cardiomyocyte viability by suppressing transcription factor EB expression and disrupting autophagy.

Doxorubicin (DOX) is an effective anti-cancer agent. However, DOX treatment increases patient susceptibility to dilated cardiomyopathy. DOX predisposes cardiomyocytes to insult by suppressing mitochondrial energy metabolism, altering calcium flux, and disrupting proteolysis and proteostasis.

Glucolipotoxicity diminishes cardiomyocyte TFEB and inhibits lysosomal autophagy during obesity and diabetes.

Impaired cardiac metabolism in the obese and diabetic heart leads to glucolipotoxicity and ensuing cardiomyopathy. Glucolipotoxicity causes cardiomyocyte injury by increasing energy insufficiency, impairing proteasomal-mediated protein degradation and inducing apoptosis. Proteasome-evading proteins are degraded by autophagy in the lysosome, whose metabolism and function are regulated by master regulator transcription factor EB (TFEB).

Cardioprotective effect of Azadirachta indica A. Juss. on isoprenaline induced myocardial infarction in rats.

The present study was designed to evaluate the cardioprotective potential of aqueous leaf extract of Azadirachta indica A. Juss. (AI) on the basis of haemodynamic, biochemical and histopathological parameters in isoprenaline induced myocardial infarction in rats and to compare with vitamin E, a known cardioprotective antioxidant.