The role of Septin 9 in regulating vascular permeability in malarial respiratory distress syndrome

Author(s)

Stefani Aparecida Minchio Rodrigues

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2024-04-11

Examining board members

Silvya Stuchi Maria Engler; Vinícius Santana Nunes

• Advisor: Sabrina Epiphanio

Abstract

Malaria is a global health problem, with 249 million cases of infection, causing 608 thousand deaths in the year 2022. Caused by the genus Plasmodium, there are five main species that cause malaria in humans, Plasmodium malariae, Plasmodium ovale, Plasmodium knowlesi, Plasmodium vivax and Plasmodium falciparum, the last two being responsible for the largest number of clinical cases and deaths around the world, transmitted by the female mosquito of the genus Anopheles during blood meal. It is also known that erythrocytes infected by Plasmodium berghei ANKA (PbA) cause changes in the actin cytoskeleton, consequently leading to hyperpermeability of the endothelial barrier. In in vitro experiments, immunofluorescence, changes in the actin cytoskeleton were observed in cells stimulated with erythrocytes parasitized by PbA (EP), in contrast, those not stimulated (NE) and stimulated with erythrocytes not parasitized by PbA (EnP), did not show changes the same. In the in vivo experiments, when observing collected data, these being respiratory (penh and respiratory frequency) and parasitemia collected on the 7th DPI, the same pattern was observed between experiment 1 and experiment 2. Animals infected with 106 infected erythrocytes were allocated into two groups, namely hyperparasitemia (HP) or malaria-associated acute respiratory distress syndrome (ARDS/ARDS-MA) and compared to those not infected (NI). NI animals do not present parasitemia, on the other hand, ARDS animals have greater parasitemia than HP animals, as the latter have an increase in their parasitemia after the 12th DPI, and thus continue to gradually increase until the animals die. the same pattern as parasitemia, NI with lower penh than HPs and ARDS, among these, the ARDS group being the highest. The respiratory rate, in turn, is higher in the NI group, with the ARDS group being lower than the HP, a finding considered normal, given that the lungs of animals with ARDS suffer greater damage than the HPs. Despite not showing a significant value, SDS-PAGE (WB) gel images show a higher concentration of Septin 9 in animals with ARDS compared to HPs and NIs. The same is observed in qRT-PCR, even without statistical significance, the value shown in the graphs has a higher concentration in ARDS. Thus, Septin 9 is present in CEPP, and, even without statistical significance, in the same way that it is present in lung tissue samples used in WB and qT-PCR. It is also hypothesized that this protein can be activated and thus undergo changes in its intracellular location. (AU)

• FAPESP's process: 22/08582-8 - The role of septin 9 in the regulation of vascular permeability in malaria-associated acute respiratory distress syndrome
• Grantee: Stefani Aparecida Minchio Rodrigues
• Support Opportunities: Scholarships in Brazil - Master