Highly Glycolytic Immortalized Human Dermal Microvascular Endothelial Cells are Able to Grow in Glucose-Starved Conditions

Abstract

Endothelial cells form the inner lining of blood vessels, in a process known as angiogenesis. Excessive angiogenesis is a hallmark of several diseases, including cancer. The number of studies in endothelial cell metabolism has increased in recent years, and new metabolic targets for pharmacological treatment of pathological angiogenesis are being proposed. In this work, we wanted to address experimental evidence of substrate (namely glucose, glutamine and palmitate) dependence in immortalized dermal microvascular endothelial cells in comparison to primary endothelial cells. In addition, due to the lack of information about lactate metabolism in this specific type of endothelial cells, we also checked their capability of utilizing extracellular lactate. For fulfilling these aims, proliferation, migration, Seahorse, substrate uptake/utilization, and mRNA/protein expression experiments were performed. Our results show a high glycolytic capacity of immortalized dermal microvascular endothelial cells, but an early independence of glucose for cell growth, whereas a total dependence of glutamine to proliferate was found. Additionally, in contrast with reported data in other endothelial cell lines, these cells lack monocarboxylate transporter 1 for extracellular lactate incorporation. Therefore, our results point to the change of certain metabolic features depending on the endothelial cell line.

New insights in the targets of action of dimethyl fumarate in endothelial cells: effects on energetic metabolism and serine synthesis in vitro and in vivo

“…DMF diminished glutamine oxidation in different EC lines (including microvascular and mesovascular ECs) and in cancer MDA-MB-231 cells. All these cell lines are known to be highly glycolytic [34][35][36] . However, DMF failed to alter glutamine oxidation in the highly glutaminedependent, oxidative cell line HeLa 37 .…”

New insights in the targets of action of dimethyl fumarate in endothelial cells: effects on energetic metabolism and serine synthesis in vitro and in vivo

“…DMF diminished glutamine oxidation in different EC lines (including microvascular and mesovascular ECs) and in cancer MDA-MB-231 cells. All these cell lines are known to be highly glycolytic [34][35][36] . However, DMF failed to alter glutamine oxidation in the highly glutaminedependent, oxidative cell line HeLa 37 .…”

Arterial Blood Pressure Features of Hypertensive Patients with Typical and Atypical 460 nm Skin Fluorescence Response to Transient Ischaemia

“…In cardiomyocytes, the mitochondrial origin of NADH may be more important for its accumulation during ischaemia. However, NADH metabolism in the skin cells may be different from cardiomyocytes [ 28 ].…”

Glutamate dehydrogenase 1 mediated glutaminolysis sustains HCC cells survival under glucose deprivation

“…Glucose and glutamine are the two main energy sources required for the rapid proliferation of tumor cells [20,21]. Notably, the occurrence and development of some cancers seem to prefer aerobic glycolysis [22.23], while others are more dependent on glutaminolysis [24,25]. Given the important role of glucose and glutamine in cell proliferation and survival, it is of great significance to clarify the relationship between glucose metabolism and glutaminolysis in HCC.…”

New insights in the targets of action of dimethyl fumarate in endothelial cells: effects on energetic metabolism and serine synthesis in vitro and in vivo

“…DMF diminished glutamine oxidation in different EC lines (including microvascular and mesovascular ECs) and in cancer MDA-MB-231 cells. All these cell lines are known to be highly glycolytic [34][35][36] . However, DMF failed to alter glutamine oxidation in the highly glutaminedependent, oxidative cell line HeLa 37 .…”

Arterial Blood Pressure Features of Hypertensive Patients with Typical and Atypical 460 nm Skin Fluorescence Response to Transient Ischaemia

“…In cardiomyocytes, the mitochondrial origin of NADH may be more important for its accumulation during ischaemia. However, NADH metabolism in the skin cells may be different from cardiomyocytes [ 28 ].…”

Glutamate dehydrogenase 1 mediated glutaminolysis sustains HCC cells survival under glucose deprivation

“…Glucose and glutamine are the two main energy sources required for the rapid proliferation of tumor cells [20,21]. Notably, the occurrence and development of some cancers seem to prefer aerobic glycolysis [22.23], while others are more dependent on glutaminolysis [24,25]. Given the important role of glucose and glutamine in cell proliferation and survival, it is of great significance to clarify the relationship between glucose metabolism and glutaminolysis in HCC.…”

New insights in the targets of action of dimethyl fumarate in endothelial cells: effects on energetic metabolism and serine synthesis in vitro and in vivo

“…DMF diminished glutamine oxidation in different EC lines (including microvascular and mesovascular ECs) and in cancer MDA-MB-231 cells. All these cell lines are known to be highly glycolytic [34][35][36] . However, DMF failed to alter glutamine oxidation in the highly glutaminedependent, oxidative cell line HeLa 37 .…”

Arterial Blood Pressure Features of Hypertensive Patients with Typical and Atypical 460 nm Skin Fluorescence Response to Transient Ischaemia

“…In cardiomyocytes, the mitochondrial origin of NADH may be more important for its accumulation during ischaemia. However, NADH metabolism in the skin cells may be different from cardiomyocytes [ 28 ].…”

Glutamate dehydrogenase 1 mediated glutaminolysis sustains HCC cells survival under glucose deprivation

“…Glucose and glutamine are the two main energy sources required for the rapid proliferation of tumor cells [20,21]. Notably, the occurrence and development of some cancers seem to prefer aerobic glycolysis [22.23], while others are more dependent on glutaminolysis [24,25]. Given the important role of glucose and glutamine in cell proliferation and survival, it is of great significance to clarify the relationship between glucose metabolism and glutaminolysis in HCC.…”