Laboratory of Signal Transduction, Department of Medical Sciences, Institute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal.
Published: November 2019
AI Article Synopsis
Article Abstract
The unfolded protein response (UPR) is involved in protein quality control and is activated in response to several stressors. Although in testis the UPR mechanisms are well described, their presence in spermatozoa is contentious. We aimed to investigate the presence of UPR-related proteins in human sperm and the impact of oxidative stress induction in UPR activation. To identify UPR-related proteins in human sperm, a bioinformatic approach was adopted. To explore the activation of UPR, sperm were exposed to hydrogen peroxide (HO) and motility, vitality, and the levels of UPR-related proteins were assessed. We identified 97 UPR-related proteins in human sperm and showed, for the first time, the presence of HSF1, GADD34, and phosphorylated eIF2α. Additionally, the exposure of human sperm to HO resulted in a significant decrease in sperm viability and motility and an increase in the levels of HSF1, HSP90, HSP60, HSP27, and eIF2α; all proteins involved in sensing and response to unfolded proteins. This study gave us a first insight into the presence of UPR mechanisms in the male gamete. However, the belief that sperm are devoid of transcription and translation highlight the need to clarify if these pathways are activated in sperm in the same way as in somatic cells.
A mounting body of evidence suggests that the endoplasmic reticulum stress and the unfolded protein response are involved in the underlying mechanisms responsible for vascular diseases. Inositol-requiring protein 1α (IRE1α), the most ancient branch among the UPR-related signaling pathways, can possess both serine/threonine kinase and endoribonuclease (RNase) activity and can perform physiological and pathological functions. The IRE1α-signaling pathway plays a critical role in the pathology of various vascular diseases.
Extracellular signal-regulated kinase 5 (ERK5), a mitogen-activated protein kinase (MAPK) family member, plays an important role in various biological processes, such as proliferation, apoptosis, differentiation, survival, and cell regulation. However, studies on the effects of ERK5 on porcine preimplantation embryos are limited. In this study, to determine the function of ERK5 during porcine embryo development, ERK5 function was inhibited by adding the ERK5 inhibitor JWG-071.
Background: The unfolded protein response (UPR) is a critical biological process related to a variety of physiological functions and cardiac disease. However, the role of UPR-related genes in acute myocardial infarction (AMI) has not been well characterized. Therefore, this study aims to elucidate the mechanism and role of the UPR in the context of AMI.
The study investigates the role of DEPTOR, an mTOR inhibitor, in asthma pathogenesis, revealing decreased DEPTOR expression in asthma models.*
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Overexpression of DEPTOR reduces airway inflammation and mucus production while inhibiting ER stress markers and inflammatory factors in both an animal model and cell cultures.*
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SOD1, identified as a downstream factor of DEPTOR, plays a significant role in mitigating asthma symptoms, indicating that DEPTOR may improve asthma by regulating ER stress through SOD1.*
The study explores how overexpressing FGF23 affects SaOS-2 cells, particularly regarding stress responses and morphology, and its relation to skeletal disorders like X-linked hypophosphatemia (XLH).
Researchers utilized transmission electron microscopy and protein analysis to observe changes in the rough endoplasmic reticulum (rER) and mitochondria of these cells, noting significant alterations such as enlargement and increased contact zones.
The findings indicate higher rates of apoptosis and activation of pathways related to cellular stress, suggesting that FGF23 overexpression plays a critical role in how cells manage protein synthesis demands and stress, paving the way for potential therapeutic strategies for related diseases.
