autophagy and heat shock protein

As the stress-inducible isoform of the Heat Shock Protein 90 (HSP90), the HSP90AA1 gene encodes HSP90α and plays an important role in heat stress (HS) response. Therefore, this study aimed to investigate the role of the HSP90AA1 gene in cellular responses during HS and to identify functional single nucleotide polymorphisms (SNP) associated with thermotolerance in Holstein cattle. For the in vitro validation experiment of acute HS, cells from the Madin-Darby bovine kidney (MDBK) cell line were exposed to 42°C for 1 h, and various parameters were assessed, including cell apoptosis, cell autophagy, and the cellular functions of HSP90α by using its inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)...

To protect vulnerable populations during heat waves, public health agencies recommend maintaining indoor air temperature below ~24-28°C. While we recently demonstrated that maintaining indoor temperatures ≤26°C mitigates the development of hyperthermia and cardiovascular strain in older adults, the cellular consequences of prolonged indoor heat stress are poorly understood. We therefore evaluated the cellular stress response in 16 adults (6 females) aged 66-78 years during 8 hours rest in ambient conditions simulating homes maintained at 22°C (control) and 26°C (indoor temperature upper limit proposed by health agencies), as well as non-air-conditioned domiciles during hot weather and heat waves (31 and 36°C, respectively; all 45% relative humidity)...

Heat shock proteins (HSPs) are developmentally conserved families of protein found in both prokaryotic and eukaryotic organisms. HSPs are engaged in a diverse range of physiological processes, including molecular chaperone activity to assist the initial protein folding or promote the unfolding and refolding of misfolded intermediates to acquire the normal or native conformation and its translocation and prevent protein aggregation as well as in immunity, apoptosis, and autophagy. These molecular chaperonins are classified into various families according to their molecular size or weight, encompassing small HSPs (e...

The need for naturally occurring constituents is driven by the rise in the cancer prevalence and the unpleasant side effects associated with chemotherapeutics. Triptolide, the primary active component of "Tripterygium Wilfordii", has exploited for biological mechanisms and therapeutic potential against various tumors. Based on the recent pre-clinical investigations, triptolide is linked to the induction of death of cancerous cells by triggering cellular apoptosis via inhibiting heat shock protein expression (HSP70), and cyclin dependent kinase (CDKs) by up regulating expression of P21...

Triple-negative breast cancer (TNBC) is associated with a poor prognosis and metastatic growth. TNBC cells frequently undergo macroautophagy/autophagy, contributing to tumor progression and chemotherapeutic resistance. ANXA2 (annexin A2), a potential therapeutic target for TNBC, has been reported to stimulate autophagy. In this study, we investigated the role of ANXA2 in autophagic processes in TNBC cells. TNBC patients exhibited high levels of ANXA2, which correlated with poor outcomes. ANXA2 increased LC3B-II levels following bafilomycin A1 treatment and enhanced autophagic flux in TNBC cells...

Hypoxia-inducible factor 1 (HIF1) is critically important for driving angiogenesis and tumorigenesis. Linear ubiquitin chain assembly complex (LUBAC), the only known ubiquitin ligase capable of catalyzing protein linear ubiquitination to date, is implicated in cell signaling and associated with cancers. However, the role and mechanism of LUBAC in regulating the expression and function of HIF1α, the labile subunit of HIF1, remain to be elucidated. Herein we showed that LUBAC increases HIF1α protein expression in cultured cells and tissues of human lung cancer and enhances HIF1α DNA-binding and transcriptional activities, which are dependent upon LUBAC enzymatic activity...

Plants can be primed to withstand otherwise lethal heat stress (HS) through exposure to a foregoing temporary and mild HS, commonly known as the ´thermopriming stimulus´. Plants can also generate memories of a previous stress encounter and reset their physiology to the original cellular state once the stress has vanished. The priming stimulus triggers a widespread change of transcripts, proteins, and metabolites, which is crucial for maintaining the memory state but may not be required for growth and development under optimal conditions or may even be hurtful...

This study aimed to determine whether Thrombospondin-1 (TSP-1) can be used as a biomarker to diagnose early osteoarthritis (OA) and whether it has a chondroprotective effect against OA. We examined TSP-1 expression in cartilage, synovial fluid, and serum at different time points after anterior cruciate ligament transection (ACLT) surgery in rats. Subsequently, TSP-1 was overexpressed or silenced to detect its effects on extracellular matrix (ECM) homeostasis, autophagy level, proliferation and apoptosis in chondrocytes...

BACKGROUND: The mortality rate of colorectal cancer (CRC) ranks second worldwide. Previous research had indicated that licochalcone A (LA) was a flavonoid in licorice with diverse anticancer effects. We explored the underlying mechanisms of LA-triggered anticancer activity in CRC. METHODS: Thiazolyl Blue (MTT) experiment and EdU staining were utilized to evaluate cell proliferation. Meanwhile, cells were stained by Annexin V/PI to investigate apoptosis through flow cytometry assay...

Chaperone-mediated autophagy (CMA) is a lysosomal-dependent proteolysis pathway for the degradation of cytosolic proteins. However, exploiting CMA-mediated proteolysis to degrade proteins of interest in cancer therapy has not been widely applied. In this study, we develop a CMA-targeting chimera (CMATAC) to efficiently and specifically degrade signal transduction and activator of transcription 3 (STAT3) in tumor cells. CMATAC consists of STAT3 and heat shock cognate 70 kDa protein (HSC70) targeting peptides connected by a linker...

Autophagy is a crucial cytoprotective mechanism preventing the accumulation of cellular damage, especially during external stimuli such as cold exposure. Older adults poorly tolerate cold exposure and age-related impairments in autophagy may contribute to the associated reductions in cold tolerance. The purpose of this investigation is to evaluate the effect of different intensities of in vivo cold-water immersion and in vitro cold exposure on autophagic and apoptotic signaling in young and older males. Peripheral blood mononuclear cells (PBMCs) are isolated at baseline, end-cold exposure, and after 3 h of thermoneutral recovery...

Ferroptosis, characterized by iron accumulation and lipid peroxidation, is a form of iron-driven cell death. Mitophagy is a type of selective autophagy, where degradation of damaged mitochondria is the key mechanism for maintaining mitochondrial homeostasis. Additionally, Chaperone-mediated autophagy (CMA) is a biological process that transports individual cytoplasmic proteins to lysosomes for degradation through companion molecules such as heat shock proteins. Research has demonstrated the involvement of ferroptosis, mitophagy, and CMA in the pathological progression of Osteoarthritis (OA)...

BACKGROUND: Mutations to the co-chaperone protein BAG3 (B-cell lymphoma-2-associated athanogene-3) are a leading cause of dilated cardiomyopathy (DCM). These mutations often impact the C-terminal BAG domain (residues 420-499), which regulates heat shock protein 70-dependent protein turnover via autophagy. While mutations in other regions are less common, previous studies in patients with DCM found that co-occurrence of 2 BAG3 variants (P63A, P380S) led to worse prognosis. However, the underlying mechanism for dysfunction is not fully understood...

In this work, we describe a novel ruthenium-xanthoxylin complex, [Ru(phen)2 (xant)](PF6 ) (RXC), that can eliminate colorectal cancer (CRC) stem cells by targeting the chaperone Hsp90. RXC exhibits potent cytotoxicity in cancer cell lines and primary cancer cells, causing apoptosis in HCT116 CRC cells, as observed by cell morphology, YO-PRO-1/PI staining, internucleosomal DNA fragmentation, mitochondrial depolarization, and PARP cleavage (Asp214). Additionally, RXC can downregulate the HSP90AA1 and HSP90B1 genes and the expression of HSP90 protein, as well as the expression levels of its downstream/client elements Akt1, Akt (pS473), mTOR (pS2448), 4EBP1 (pT36/pT45), GSK-3β (pS9), and NF-κB p65 (pS529), implying that these molecular chaperones can be molecular targets for RXC...

Cisplatin, a classical platinum-based chemotherapy agent, has been a frontline treatment for various cancers for decades. However, its effectiveness has been hindered by the development of resistance, leading to cancer relapse. Addressing this challenge is crucial for both clinical practice and research. Hence, the imperative to unravel the intricate mechanisms underpinning cisplatin resistance and to uncover novel strategies to overcome this barrier holds immense significance. Within this review, we summarized the classification of platinum agents, highlighting their roles in therapeutic landscapes...

Isoflurane, a widely used inhalation anesthetic in clinical practice, is associated with an increased risk of neuronal injury. Heat shock protein 90 (HSP90) plays a crucial role in maintaining neuronal homeostasis under stress conditions; however, its role during isoflurane exposure remains poorly understood. In this study, we aimed to investigate the protective effects of HSP90 inhibition and explore the regulatory mechanisms underlying these effects during isoflurane exposure. We found that the HSP90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17 AAG) has great protective effects in mitigating isoflurane-induced ferroptosis of mouse hippocampus and cultured neuronal cells...

Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by abnormal α-synuclein misfolding and aggregation, mitochondrial dysfunction, oxidative stress, as well as progressive death of dopaminergic neurons in the substantia nigra. Molecular chaperones play a role in stabilizing proteins and helping them achieve their proper structure. Previous studies have shown that overexpression of heat shock protein 90 (HSP90) can lead to the death of dopaminergic neurons associated with PD...

The tripartite interaction motif (TRIM) family of proteins is known for their antiviral activity through different mechanisms, such as interfering with viral components, regulating immune responses, and participating in autophagy-mediated defense pathways. In this study, we investigated the role of tripartite interaction motif 26 (TRIM26), which is encoded by a major histocompatibility complex (MHC) gene, in regulating Epstein-Barr virus (EBV) infection of nasopharyngeal epithelial cells. We found that TRIM26 expression was induced upon EBV infection and that it indirectly targeted EphA2, a crucial epithelial receptor for EBV entry...

BACKGROUND: In the past few years, immunotherapies of hepatocellular carcinoma (HCC) targeting programmed cell death protein 1 (PD-1) and its ligand programmed cell death ligand 1 (PD-L1), have achieved durable clinical benefits. However, only a fraction of HCC patients showed objective clinical response to PD-1/PD-L1 blockade alone. Despite the impact on post-translational modifications of PD-L1 being substantial, its significance in resistance to HCC immunotherapy remains poorly defined...

The A. japonicus industry has expanded significantly, but no research has focused on determining the age of A. japonicus during farming. Correctly estimating the age of A. japonicus can provide a decision-making basis for the breeding process and data for the protection of A. japonicus aquatic germplasm resources. DNA methylation levels in the body wall of Apostichopus japonicus at 4 months, 1 year, 2 years, and 3 years old were determined using MethylRAD-Seq, and differentially methylated genes were screened...