scholarly journals Heat Shock Factor 1 Prevents Age-Related Hearing Loss by Decreasing Endoplasmic Reticulum Stress

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2454
Author(s):  
Yun Yeong Lee ◽  
Eun Sol Gil ◽  
In Hye Jeong ◽  
Hantai Kim ◽  
Jeong Hun Jang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Heat Shock ◽  
Er Stress ◽  
High Frequency ◽  
Caspase 3 ◽  
Frequency Region ◽  
Heat Shock Factor 1 ◽  
High Frequency Region ◽  
Age Related ◽  
Age Related Hearing Loss

Endoplasmic reticulum (ER) stress is a common stress factor during the aging process. Heat shock factor 1 (HSF1) plays a critical role in ER stress; however, its exact function in age-related hearing loss (ARHL) has not been fully elucidated. The purpose of the present study was to identify the role of HSF1 in ARHL. In this study, we demonstrated that the loss of inner and outer hair cells and their supporting cells was predominant in the high-frequency region (basal turn, 32 kHz) in ARHL cochleae. In the aging cochlea, levels of the ER stress marker proteins p-eIF2α and CHOP increased as HSF1 protein levels decreased. The levels of various heat shock proteins (HSPs) also decreased, including HSP70 and HSP40, which were markedly downregulated, and the expression levels of Bax and cleaved caspase-3 apoptosis-related proteins were increased. However, HSF1 overexpression showed significant hearing protection effects in the high-frequency region (basal turn, 32 kHz) by decreasing CHOP and cleaved caspase-3 and increasing the HSP40 and HSP70 proteins. These findings were confirmed by HSF1 functional studies using an auditory cell model. Therefore, we propose that HSF1 can function as a mediator to prevent ARHL by decreasing ER stress-dependent apoptosis in the aging cochlea.

scholarly journals P0015SIRT2 REGULATES CISPLATIN-INDUCED ENDOPLASMIC RETICULUM STRESS THROUGH HEAT SHOCK FACTOR 1 DEACETYLATION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Woong Park ◽  
Hyeongwan Kim ◽  
Yujin Jung ◽  
Kyung Pyo Kang ◽  
Won Kim
Keyword(s):  
Endoplasmic Reticulum ◽  
Heat Shock ◽  
Er Stress ◽  
Knockout Mice ◽  
Malignant Tumors ◽  
Heat Shock Factor ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Heat Shock Factor 1 ◽  
Caspase 12

Abstract Background and Aims Nephrotoxicity is an important cisplatin-induced adverse reaction and restricts the use of cisplatin to treat malignant tumors. Endoplasmic reticulum (ER) stress is caused by the accumulation of misfolded proteins, and is induced by cisplatin in kidneys. SIRT2 nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase is a member of the sirtuin family, but its role in cisplatin-induced ER stress remains unclear. Method To investigate the effect of SIRT2 on cisplatin-induced ER stress using SIRT2 knockout mice and human proximal tubular epithelial cells (HK-2 cells). We treated cisplatin (20 µg/mL) or induced by intraperitoneal injection of cisplatin (20 mg/kg) and evaluated the changes of ER stress and its signal mechanism. Results Cisplatin administration was found to significantly increase the expressions of PRKR-like ER kinase (PERK), phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), and the C/EBP homologous protein (CHOP) and caspase-12 in the kidneys of SIRT2-wild type mice. However, cisplatin-induced increases in the expressions of p-PERK, p-eIF2α, CHOP and, caspase-12 were diminished in kidneys of SIRT2 knockout mice. In vitro, cisplatin significantly increased the expressions of p-PERK, p-eIF2α, CHOP, and caspase-12 in HK-2 cells. When the effect of SIRT2 on cisplatin-induced ER stress was evaluated using SIRT2-siRNA (ON-TARGET plus human SIRT2 siRNA) or the SIRT2 inhibitors, AGK2 and AK1, knockdown or inhibition of SIRT2 significantly attenuated the cisplatin-induced protein expression of p-PERK, p-eIF2α, CHOP, and caspase-12. Immunoprecipitation studies showed SIRT2 bound physically to heat shock factor (HSF)1 and that HSF1 acetylation was significantly increased by cisplatin. In addition, knockdown of SIRT2 increased cisplatin-induced HSF1 acetylation and increased the expression of heat shock protein (HSP)70. Conclusion These observations suggest that suppression of SIRT2 ameliorates cisplatin-induced ER stress by increasing HSF1 acetylation and HSP expression.

Anderson-Stuart Model to Analyze AC and DC Conductivity of Lithium Zinc-Silicate Glass / Glass-Ceramics

2007 ◽  
Vol 280-283 ◽  
pp. 919-924
Author(s):  
M.S. Jogad ◽  
V.K. Shrikhande ◽  
A.H. Dyama ◽  
L.A. Udachan ◽  
Govind P. Kothiyal
Keyword(s):  
High Frequency ◽  
Glass Ceramics ◽  
Low Frequency ◽  
Frequency Region ◽  
Dc Conductivity ◽  
Frequency Range ◽  
High Frequency Region ◽  
Dc Conductivities ◽  
Conductivity Variation ◽  
Different Temperatures

AC and DC conductivities have been measured by using the real (e¢) and imaginary (e¢¢) parts of the dielectric constant data of glass and glass-ceramics (GC) at different temperatures in the rage 297-642K and in the frequency range 100 Hz to 10 MHz. Using Anderson –Stuart model, we have calculated the activation energy, which is observed to be lower than that of the DC conductivity. The analysis for glass/glass-ceramics indicates that the conductivity variation with frequency exhibits an initial linear region followed by nonlinear region with a maximum in the high-frequency region. The observed frequency dependence of ionic conductivity has been analyzed within the extended Anderson–Stuart model considering both the electrostatic and elastic strain terms. In glass/glassceramic the calculations based on the Anderson-Stuart model agree with the experimental observations in the low frequency region but at higher frequencies there is departure from measured data.

Channel thermal noise of SOI MOSFET in high-frequency region

2005 ◽  
Vol 20 (2) ◽  
pp. 216-220
Author(s):  
Nirupama Kapoor ◽  
Subhasis Haldar ◽  
Mridula Gupta ◽  
R S Gupta
Keyword(s):  
High Frequency ◽  
Thermal Noise ◽  
Frequency Region ◽  
High Frequency Region ◽  
Soi Mosfet

Further Observations on Noise Levels in Infant Incubators

PEDIATRICS ◽  
1979 ◽  
Vol 63 (1) ◽  
pp. 100-106 ◽  
Author(s):  
Fred H. Bess ◽  
Barbara Finlayson Peek ◽  
Judy J. Chapman
Keyword(s):  
High Frequency ◽  
Impulse Noise ◽  
Life Support ◽  
Acoustic Analysis ◽  
Frequency Region ◽  
Noise Levels ◽  
Storage Unit ◽  
High Frequency Region ◽  
Different Types ◽  
Opening And Closing

The purpose of this study was to conduct an acoustic analysis of incubator noise under two conditions: when the incubator was associated with different types of life-support equipment; and when impulse noise was created by striking the side of the incubator or by opening and closing the doors of the storage unit. It was found that the life-support equipment increased the overall noise levels of incubators by as much as 15 to 20 dB. Much of this increased energy was in the high frequency region. Impulse signals created by striking the side of the incubator ranged from 130 to 140 dB. A representative impulse for opening the incubator was 92.8 dB, whereas closing the door produced a peak amplitude of 114 dB.

scholarly journals The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases

2020 ◽  
Vol 21 (6) ◽  
pp. 2108 ◽  
Author(s):  
Wioletta Rozpędek-Kamińska ◽  
Natalia Siwecka ◽  
Adam Wawrzynkiewicz ◽  
Radosław Wojtczak ◽  
Dariusz Pytel ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Neurodegenerative Diseases ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Stress Conditions ◽  
World Population ◽  
Dependent Manner ◽  
Age Related ◽  
The Unfolded Protein Response

Higher prevalence of neurodegenerative diseases is strictly connected with progressive aging of the world population. Interestingly, a broad range of age-related, neurodegenerative diseases is characterized by a common pathological mechanism—accumulation of misfolded and unfolded proteins within the cells. Under certain circumstances, such protein aggregates may evoke endoplasmic reticulum (ER) stress conditions and subsequent activation of the unfolded protein response (UPR) signaling pathways via the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-dependent manner. Under mild to moderate ER stress, UPR has a pro-adaptive role. However, severe or long-termed ER stress conditions directly evoke shift of the UPR toward its pro-apoptotic branch, which is considered to be a possible cause of neurodegeneration. To this day, there is no effective cure for Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), or prion disease. Currently available treatment approaches for these diseases are only symptomatic and cannot affect the disease progression. Treatment strategies, currently under detailed research, include inhibition of the PERK-dependent UPR signaling branches. The newest data have reported that the use of small-molecule inhibitors of the PERK-mediated signaling branches may contribute to the development of a novel, ground-breaking therapeutic approach for neurodegeneration. In this review, we critically describe all the aspects associated with such targeted therapy against neurodegenerative proteopathies.

Carrier-envelope-phase effect on laser-driven bound-bound transitions in the high-frequency region

2012 ◽  
Vol 86 (4) ◽  
Author(s):  
Zhen Zhai ◽  
Dian Peng ◽  
Xi Zhao ◽  
Fuming Guo ◽  
Yujun Yang ◽  
...  
Keyword(s):  
High Frequency ◽  
Frequency Region ◽  
Phase Effect ◽  
High Frequency Region ◽  
Carrier Envelope Phase

New data on the kaolinite-potassium acetate complex

Clay Minerals ◽  
1999 ◽  
Vol 34 (4) ◽  
pp. 565-577 ◽  
Author(s):  
M. D. Ruiz Cruz ◽  
F. I. Franco Duro
Keyword(s):  
High Frequency ◽  
Electrostatic Interactions ◽  
Potassium Acetate ◽  
Frequency Region ◽  
Basal Spacing ◽  
Intercalation Complex ◽  
High Frequency Region ◽  
Oh Groups ◽  
Acetate Complex ◽  
Inner Surface

AbstractThe intercalation complex of kaolinite and potassium acetate (KAc) was studied by HTXRD, IR spectroscopy and DTA-TG. The HTXRD patterns indicate that the 14.06 Å basal spacing of the complex contracts to 11.77 Å and 9.35 Å after heating at 60°C. The DTA-TG data indicate that water is present in these new complexes, the decomposition of which occurs between 290°C and 400°C. Modifications observed in the high-frequency region of the spectra obtained after heating suggest that K ions occupy the ditrigonal holes in the OH surface of the kaolinite layers, whereas water is probably located between the KAc layer and the OH surface of the kaolinite. This structural arrangement would favour the H-bonding between inner-surface OH groups and water and justifies the presence of new bands at lower frequencies. Electrostatic interactions between the keyed K ions and O of the inner OH groups would justify the modifications of the 3619 cm-1 OH-stretching band.

scholarly journals Autophagy activated via GRP78 to alleviate endoplasmic reticulum stress for cell survival in blue light-mediated damage of A2E-laden RPEs

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jingyang Feng ◽  
Yuhong Chen ◽  
Bing Lu ◽  
Xiangjun Sun ◽  
Hong Zhu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Signaling Pathway ◽  
Blue Light ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Degenerative Diseases ◽  
Caspase 12 ◽  
Age Related ◽  
Retinal Degenerative Diseases

Abstract Background Retinal pigment epithelium cells (RPEs) are critical for maintaining retinal homeostasis. Accumulation of age-related lipofuscin, N-retinylidene-N-retinylethanolamine (A2E), makes RPEs vulnerable to blue light-mediated damage, which represents an initial cause of some retinal degenerative diseases. This study investigated the activation of autophagy and the signaling pathway involved in glucose-related protein 78 (GRP78) induced autophagy in blue light-mediated damage of A2E-laden RPEs. In addition, we explored whether autophagy could play a protective role by alleviating endoplasmic reticulum (ER) stress to promote RPEs survival. Methods RPEs were incubated with 25 μM A2E for 2 h and exposed to blue light for 20 min. The expression of ER stress-related apoptotic proteins, CHOP and caspase-12, as well as autophagy marker LC3 were measured by western blot analysis. Autophagosomes were observed by both transmission electron microscopy and immunofluorescence assays. GRP78 interference performed by short hairpin RNA (shRNA) was used to identify the signaling pathway involved in GRP78 induced autophagy. Cell death was assessed using TUNEL analysis. Results Treatment with A2E and blue light markedly increased the expression of ER stress-related apoptotic molecules CHOP and caspase-12. The activation of autophagy was recognized by observing autophagosomes at ultrastructural level. Additionally, punctate distributions of LC3 immunofluorescence and enhanced conversions of LC3-I to LC3-II were found in A2E and blue light-treated RPEs. Moreover, GRP78 interference reduced AMPK phosphorylation and promoted mTOR activity, thereby downregulating autophagy. In addition, the inhibition of autophagy made RPEs vulnerable to A2E and blue light damage. In contrast, the autophagy inducer rapamycin alleviated ER stress to promote RPEs survival. Conclusions GRP78 activates autophagy via AMPK/mTOR in blue light-mediated damage of A2E-laden RPEs in vitro. Autophagy may be a vital endogenous cytoprotective process to alleviate stress for RPEs survival in retinal degenerative diseases.

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