TARDBP and C9orf72 mutations in this cohort were similar to those found in other centres worldwide. VAPB mutation (P56S) was highly prevalent in Brazilian FALS patients.
BackgroundThe testis-specific isoform of angiotensin-converting enzyme (tACE) is exclusively expressed in germ cells during spermatogenesis. Although the exact role of tACE in male fertility is unknown, it clearly plays a critical function in spermatogenesis. The dipeptidase domain of tACE is identical to the C-terminal catalytic domain of somatic ACE (sACE). Bradykinin potentiating peptides (BPPs) from snake venoms are the first natural sACE inhibitors described and their structure–activity relationship studies were the basis for the development of antihypertensive drugs such as captopril. In recent years, it has been showed that a number of BPPs – including BPP-10c – are able to distinguish between the N- and C-active sites of sACE, what is not applicable to captopril. Considering the similarity between tACE and sACE (and since BPPs are able to distinguish between the two active sites of sACE), the effects of the BPP-10c and captopril on the structure and function of the seminiferous epithelium were characterized in the present study. BPP-10c and captopril were administered in male Swiss mice by intraperitoneal injection (4.7 μmol/kg for 15 days) and histological sections of testes were analyzed. Classification of seminiferous tubules and stage analysis were carried out for quantitative evaluation of germ cells of the seminiferous epithelium. The blood-testis barrier (BTB) permeability and distribution of claudin-1 in the seminiferous epithelium were analyzed by hypertonic fixative method and immunohistochemical analyses of testes, respectively.ResultsThe morphology of seminiferous tubules from animals treated with BPP-10c showed an intense disruption of the epithelium, presence of atypical multinucleated cells in the lumen and degenerated germ cells in the adluminal compartment. BPP-10c led to an increase in the number of round spermatids and total support capacity of Sertoli cell in stages I, V, VII/VIII of the seminiferous epithelium cycle, without affecting BTB permeability and the distribution of claudin-1 in the seminiferous epithelium. Interestingly, no morphological or morphometric alterations were observed in animals treated with captopril.ConclusionsThe major finding of the present study was that BPP-10c, and not captopril, modifies spermatogenesis by causing hyperplasia of round spermatids in stages I, V, and VII/VIII of the spermatogenic cycle.
Thimet oligopeptidase (
EC 3.4.24.15
,
TOP
) is a cytosolic mammalian zinc protease that can process a diversity of bioactive peptides.
TOP
has been pointed out as one of the main postproteasomal enzymes that process peptide antigens in the
MHC
class I presentation route. In the present study, we describe a fine regulation of
TOP
activity by hydrogen peroxide (H
2
O
2
). Cells from a human embryonic kidney cell line (
HEK
293) underwent an ischemia/reoxygenation‐like condition known to increase H
2
O
2
production. Immediately after reoxygenation,
HEK
293 cells exhibited a 32% increase in
TOP
activity, but no
TOP
activity was observed 2 h after reoxygenation. In another model, recombinant rat
TOP
(
rTOP
) was challenged by H
2
O
2
produced by rat liver mitoplasts (
RLM
t) alone, and in combination with antimycin A, succinate, and antimycin A plus succinate. In these conditions,
rTOP
activity increased 17, 30, 32 and 38%, respectively. Determination of H
2
O
2
concentration generated in reoxygenated cells and mitoplasts suggested a possible modulation of
rTOP
activity dependent on the concentration of H
2
O
2
. The measure of pure
rTOP
activity as a function of H
2
O
2
concentration corroborated this hypothesis. The data fitted to an asymmetrical bell‐shaped curve in which the optimal activating H
2
O
2
concentration was 1.2
nM
, and the maximal inhibition (75% about the control) was 1 μ
m
. Contrary to the oxidation produced by aging associated with enzyme oligomerization and inhibition, H
2
O
2
oxidation produced sulfenic acid and maintained
rTOP
in the monomeric form. Consistent with the involvement of
rTOP
in a signaling redox cascade, the H
2
O
2
‐oxidized
rTOP
reacted with dimeric thioredoxin‐1 (
TR
x‐1) and remained covalently bound to one subunit of TRx‐1.
BackgroundConsidering the similarity between the testis-specific isoform of angiotensin-converting enzyme and the C-terminal catalytic domain of somatic ACE as well as the structural and functional variability of its natural inhibitors, known as bradykinin-potentiating peptides (BPPs), the effects of different synthetic peptides, BPP-10c (
O testículo de mamíferos é um órgão suscetível a agentes tóxicos ambientais ou terapêuticos que comprometem a espermatogênese, e a análise dos túbulos seminíferos (parâmetros morfológicos e morfométricos) é uma estratégia simples para avaliar alterações nesse processo. Assim, as estratégias de coleta, fixação e coloração da amostra biológica (tecido) são fundamentais para preservar as características morfológicas e garantir a eficácia da análise e precisão do diagnóstico. Entretanto, a fixação do material biológico é uma das etapas mais críticas na preparação histológica, principalmente no testículo. O objetivo, neste trabalho, foi avaliar diferentes estratégias de fixação do testículo para padronizar uma técnica adequada às análises morfológicas do epitélio seminífero de ratos. Ratos da linhagem Wistar foram sacrificados, e os testículos, coletados em diferentes protocolos de fixação. A perfusão com glutaraldeído 4% e inclusão do tecido pela técnica de historesina foram considerados os métodos mais apropriados para realizar o processamento histológico, pois a morfologia dos túbulos seminíferos e o compartimento intersticial foram preservados.
Unfortunately, the original version of this article [1] contained an error. The conclusion was included incorrectly. The conclusion has been corrected in the original article and is also included correctly below.
ConclusionOverall, the results obtained from the proline-rich snake-venom oligopeptide suggest that the alterations in the structure of the seminiferous epithelium in mice following BPP-10c and BPP-AP treatment, but not treatment with BPP-11e, are dependent on their primary molecular structure. This study offers new perspectives for the elucidation of possible mechanisms involved in the impairment of spermatogenesis by BPP-10c and BPP-AP, thereby providing new insight into the biological features of the snake venom.
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