Glucose transporters regulation on ischemic brain: possible role as therapeutic target.
Ischemic stroke is a major cause of death worldwide that provokes a high society cost. Deprivation of blood supply, with the subsequent deficiency of glucose and oxygen, triggers an important number of mechanisms (e.g. excitotoxicity, oxidative stress and inflammation) leading to irreversible neuronal injury. Consequently, ischemia increases the energy demand which is associated with profound changes in brain energy metabolism. Glucose transport activity may adapt to ensure the delivery of glucose to maintain normal cellular function, even at the low glucose levels observed in plasma during ischemia. In the brain, the main glucose transporters (GLUTs) are GLUT3 in neurons and GLUT1 in the microvascular endothelial cells of the blood brain barrier and glia. The intracellular signaling pathways involved in GLUT regulation in cerebral ischemia remain unclear; however, it has been established that ischemia induces changes in their expression. In this review, we describe the effect of glutamate-induced excitotoxicity, mitochondrial damage, glucose deprivation, and hypoxia on GLUTs expression in the brain. Additionally, we discuss the possible role of GLUTs as therapeutic target for ischemia. Despite of the intense research, current therapeutics options for stroke are very limited, therefore it is especially important to find new options. Few studies have examined the neuroprotective potential of GLUT up-regulation in ischemic stroke; however, evidence suggests that augmented GLUTs could be related to a protective mechanism. Increased understanding of the beneficial effects of GLUTs activation provides the rationale for targeting GLUT in the development of new therapeutic strategies.
Espinoza-Rojo
Mónica
M
Laboratorio de Biología Molecular y Genómica, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México.
Iturralde-Rodríguez
Karen Ivonne
KI
Chánez-Cárdenas
María-Elena
ME
Ruiz-Tachiquín
Martha Eugenia
ME
Aguilera
Penélope
P
D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004967:Estrogens / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005737:Garlic / Q000737:chemistry; D005947:Glucose / Q000172:deficiency / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism*; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D019194:Ischemic Preconditioning; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D014810:Vitamin E / Q000494:pharmacology
D004967:Estrogens; D018690:Excitatory Amino Acid Agonists; D051246:Glucose Transport Proteins, Facilitative; D010936:Plant Extracts; D014810:Vitamin E; D018698:Glutamic Acid; D005947:Glucose