Title:Endothelin Receptors, Mitochondria and Neurogenesis in Cerebral Ischemia
Volume: 14
Issue: 6
Author(s): Anil Gulati
Affiliation:
Keywords:
Cerebral ischemia, endothelin, ETB receptor, mitochondria, neurogenesis, nerve growth factor, vascular endothelial
growth factor.
Abstract: Background: Neurogenesis is most active during pre-natal development, however, it
persists throughout the human lifespan. The putative role of mitochondria in neurogenesis and
angiogenesis is gaining importance. Since, ETB receptor mediated neurogenesis and angiogenesis has
been identified, the role of these receptors with relevance to mitochondrial functions is of interest.
Methods: In addition to work from our laboratory, we undertook an extensive search of bibliographic
databases for peer-reviewed research literature. Specific technical terms such as endothelin, mitochondria
and neurogenesis were used to seek out and critically evaluate literature that was relevant.
Results: The ET family consists of three isopeptides (ET-1, ET-2 and ET-3) that produce biological actions by acting on
two types of receptors (ETA and ETB). In the central nervous system (CNS) ETA receptors are potent constrictors of the
cerebral vasculature and appear to contribute in the causation of cerebral ischemia. ETA receptor antagonists have been
found to be effective in animal model of cerebral ischemia; however, clinical studies have shown no efficacy.
Mitochondrial functions are critically important for several neural development processes such as neurogenesis, axonal
and dendritic growth, and synaptic formation. ET appears to impair mitochondrial functions through activation of ETA
receptors. On the other hand, blocking ETB receptors has been shown to trigger apoptotic processes by activating intrinsic
mitochondrial pathway. Mitochondria are important for their role in molecular regulation of neurogenesis and
angiogenesis. Stimulation of ETB receptors in the adult ischemic brain has been found to promote angiogenesis and
neurogenesis mediated through vascular endothelial growth factor and nerve growth factor. It will be interesting to
investigate the effect of ETB receptor stimulation on mitochondrial functions in the CNS following cerebral ischemia.
Conclusion: The findings of this review implicate brain ETB receptors in angiogenesis and neurogenesis following
cerebral ischemia, it is possible that the positive effect of stimulating ETB receptors in cerebral ischemia may be mediated
through mitochondrial functions.
