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Updated: Nov 24, 2025
Sex Differences in Mouse Hippocampal Astrocytes after In-Vitro Ischemia
Published on: October 25, 2016
Sex differences exist in brain renin-angiotensin system-regulating aminopeptidase activities in transplacental
M J Ramírez-Expósito1, M P Carrera-González2, J M Martínez-Martos1
1Experimental and Clinical Physiopathology Research Group CTS-1039, Department of Health Sciences, School of Health Sciences, University of Jaén, Jaén, Spain.
Introduction:
The renin angiotensin system (RAS) is emerging as an important target for the treatment of glioma. We had described that the local RAS is involved in vivo in tumor growth in the rat model of experimental C6 glioma implanted at the subcutaneous region, through the modification of several proteolytic regulatory enzymes of aminopeptidase type.
Methods:
We analyze RAS-regulating aminopeptidase activities in plasma and brain tissue of control male and female rats and rats with transplacental ethylnitrosourea-induced gliomas.
Results:
No differences were found either the mean total number of tumors per animal or the tumor volume between male and female animals. However, we have found increased levels in aspartyl aminopeptidase in both males and females and of aminopeptidase B only in males. On the contrary, decreased levels were found in aminopeptidase N and insulin-regulated aminopeptidase activities in both males and females, whereas aminopeptidase A only decreased in females. Decreased levels of aminopeptidase N, aminopeptidase B and insulin-regulated aminopeptidase were also shown in plasma of only female rats.
Conclusions:
Under the complexity of RAS cascade, the changes found suggest the predominant actions of angiotensin III against a decreased action of angiotensin II and angiotensin IV. We conclude that angiotensin peptides are involved in tumor growth in this rat model of glioma and that their role in tumor growth can be analyzed through their corresponding proteolytic regulatory enzymes, which make them new and attractive therapeutic targets beyond the use or angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).
Insights
The renin-angiotensin system (RAS) influences glioma growth. Specific aminopeptidase changes in rats suggest angiotensin peptides are key therapeutic targets for glioma beyond current treatments.
Area of Science:
- Biochemistry
- Oncology
- Neuroscience
Background:
- The renin-angiotensin system (RAS) is implicated in glioma development.
- Local RAS activity, involving aminopeptidase enzymes, affects tumor growth.
Purpose of the Study:
- To investigate RAS-regulating aminopeptidase activities in a rat glioma model.
- To explore sex-based differences in these enzymatic activities.
Main Methods:
- Analysis of aminopeptidase activities in plasma and brain tissue.
- Comparison between control rats and rats with ethylnitrosourea-induced gliomas.
- Assessment of sex-specific differences in enzyme levels.
Main Results:
- Elevated aspartyl aminopeptidase and, in males, aminopeptidase B were observed.
- Decreased aminopeptidase N and insulin-regulated aminopeptidase activities were found in both sexes.
- Sex-specific decreases in aminopeptidase A (females) and plasma enzyme levels (females) were noted.
Conclusions:
- Angiotensin peptides are involved in glioma growth in this model.
- Aminopeptidase enzymes offer potential therapeutic targets for glioma treatment.
- These targets represent novel approaches beyond ACE inhibitors and ARBs.
