scholarly journals Overexpression of Transcripts Coding for Renin-b but Not for Renin-a Reduce Oxidative Stress and Increase Cardiomyoblast Survival under Starvation Conditions

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1204
Author(s):  
Heike Wanka ◽  
Philipp Lutze ◽  
Alexander Albers ◽  
Janine Golchert ◽  
Doreen Staar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
B Cells ◽  
Apoptotic Cell ◽  
Renin Angiotensin System ◽  
Glucose Deprivation ◽  
Protective Effects ◽  
Glucose Depletion ◽  
A Cells ◽  
Apoptosis And Necrosis

A stimulated renin-angiotensin system is known to promote oxidative stress, apoptosis, necrosis and fibrosis. Renin transcripts (renin-b; renin-c) encoding a cytosolic renin isoform have been discovered that may in contrast to the commonly known secretory renin (renin-a) exert protective effects Here, we analyzed the effect of renin-a and renin-b overexpression in H9c2 cardiomyoblasts on apoptosis and necrosis as well as on potential mechanisms involved in cell death processes. To mimic ischemic conditions, cells were exposed to glucose starvation, anoxia or combined oxygen–glucose deprivation (OGD) for 24 h. Under OGD, control cells exhibited markedly increased necrotic and apoptotic cell death accompanied by enhanced ROS accumulation, loss of mitochondrial membrane potential and decreased ATP levels. The effects of OGD on necrosis were exaggerated in renin-a cells, but markedly diminished in renin-b cells. However, with respect to apoptosis, the effects of OGD were almost completely abolished in renin-b cells but interestingly also moderately diminished in renin-a cells. Under glucose depletion we found opposing responses between renin-a and renin-b cells; while the rate of necrosis and apoptosis was aggravated in renin-a cells, it was attenuated in renin-b cells. Based on our results, strategies targeting the regulation of cytosolic renin-b as well as the identification of pathways involved in the protective effects of renin-b may be helpful to improve the treatment of ischemia-relevant diseases.

scholarly journals Apolipoprotein M is required for the protective effects of high density lipoprotein against ischemia-induced astrocyte apoptosis

2021 ◽  
Author(s):  
Xiaojia Huang ◽  
Zhiqi Zhai ◽  
Ting Zhou ◽  
Chengju Sheng ◽  
Chao Zhou ◽  
...  
Keyword(s):  
Cell Death ◽  
High Density Lipoprotein ◽  
Apoptotic Cell ◽  
Density Lipoprotein ◽  
Glucose Deprivation ◽  
High Density ◽  
Target Cells ◽  
Protective Effects ◽  
Apolipoprotein M ◽  
Sphingosine 1 Phosphate

Abstract Objectives High density lipoprotein (HDL) has been reported to show protective effects against cell death. Apolipoprotein M (ApoM) in HDL can bind with sphingosine-1-phosphate (S1P) and deliver S1P to target cells. This study aimed to evaluate the effects of HDL on astrocyte apoptosis after ischemic insult and determine the role of ApoM.Methods After ApoM-associated HDL (HDLapoM+) and ApoM-depleted HDL(HDLapoM-) were separated from mouse plasma, primary cultured mouse astrocytes were chellenged with oxygen-glucose deprivation followed by recovery in presence of HDLapoM+ or HDLapoM-. mRNA and protein samples were collected for biochemical analysis.Results The addition of HDLapoM+ attenuated apoptotic cell death in the astrocytes, but HDLapoM- did not show any effect. S1P receptor 1 (S1PR1) expression was upregulated, and specific S1PR1 inhibitor or genetic knockdown of S1pr1 abolished the protective effects. In addition, activation of Akt and ERK was induced by HDLapoM+ or free S1P, and pharmacological inhibition of Akt and ERK reduced the protection of HDLapoM+.Conclusions ApoM is essential for the protective effects of HDL, which depends on S1PR1 activation and downstream activation of Akt/ERK, Thus, ApoM may be a neuroprotective component in plasma.

scholarly journals N-Acetyl Cysteine Protects against Methamphetamine-Induced Dopaminergic Neurodegeneration via Modulation of Redox Status and Autophagy in Dopaminergic Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Prashanth Chandramani Shivalingappa ◽  
Huajun Jin ◽  
Vellareddy Anantharam ◽  
Anumantha Kanthasamy ◽  
Arthi Kanthasamy
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cell Model ◽  
Apoptotic Cell ◽  
Neuronal Cell ◽  
Redox Status ◽  
Apoptotic Cell Death ◽  
Protective Effects ◽  
Dopaminergic Cells ◽  
Dopaminergic Neurodegeneration

Methamphetamine- (MA-) induced neurotoxicity is associated with mitochondrial dysfunction and enhanced oxidative stress. Our previous study demonstrated that MA induces autophagy in a dopaminergic neuronal cell model (N27 cells). The cellular mechanisms underlying MA-induced autophagy and apoptosis remain poorly characterized. In the present study we sought to investigate the importance of GSH redox status in MA-induced neurotoxicity using a thiol antioxidant, N-acetylcysteine (NAC). Morphological and biochemical analysis revealed that MA-induced autophagy in N27 dopaminergic cells was associated with pronounced depletion of GSH levels. Moreover, pretreatment with NAC reduced MA-induced GSH depletion and autophagy, while depletion of GSH using L-buthionine sulfoximine (L-BSO) enhanced autophagy. Furthermore, treatment with NAC significantly attenuated MA-induced apoptotic cell death as well as oxidative stress markers, namely, 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE). Together, these results suggest that NAC exhibits significant protective effects against MA-induced dopaminergic cell death, presumably via modulation of the GSH level and autophagy. Collectively, our data provide mechanistic insights into the role of cellular GSH redox status in MA-induced autophagy and apoptotic cell death, and additional studies are needed to determine the therapeutic effectiveness of cellular redox modifiers in attenuating dopaminergic neurodegenerationin vivo.

Tobacco smoke induces both apoptosis and necrosis in mammalian cells: differential effects of HSP70

1998 ◽  
Vol 275 (4) ◽  
pp. L771-L779 ◽  
Author(s):  
Muriel Vayssier ◽  
Nathalie Banzet ◽  
Dominique François ◽  
Kerstin Bellmann ◽  
Barbara S. Polla
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Tobacco Smoke ◽  
Mammalian Cells ◽  
Cell Injury ◽  
Hsp70 Expression ◽  
Protective Effects ◽  
Low Concentrations ◽  
Induced Apoptosis ◽  
Apoptosis And Necrosis

Tobacco smoke (TS) has been implicated as a major risk factor in human pulmonary diseases including cancer. In this study, we used TS as a model of oxidative stress. TS-mediated oxidative stress has been shown to induce protein oxidation, DNA damage, and cell death. Here we investigated, in human and rodent cell lines, whether TS induces cell death by apoptosis or by necrosis. As described for classic oxidants, TS induced apoptosis at low concentrations and necrosis at higher concentrations. We have previously described the induction of heat shock (HS) protein (HSP) (in particular, HSP70) in human monocytes exposed to TS. HSP70 is implicated in the regulation of cell injury and cell death and, in particular, modulates apoptosis, as does the antiapoptotic oncoprotein Bcl-2. At both apoptotic and necrotic concentrations, TS induced a dose-dependent HSP70 expression, whereas Bcl-2 was induced only at necrotic concentrations. TS- or HS-induced HSP had no protective effects either on apoptosis or on necrosis, but HSP70 overexpression prevented TS-induced necrosis and consequently led to increased apoptosis. These results might reconcile the apparently contradictory data previously reported on the effects of HSP on apoptosis.

scholarly journals Kaempferol Ameliorates Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Ferroptosis by Activating Nrf2/SLC7A11/GPX4 Axis

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 923
Author(s):  
Yuan Yuan ◽  
Yanyu Zhai ◽  
Jingjiong Chen ◽  
Xiaofeng Xu ◽  
Hongmei Wang
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Antioxidant Capacity ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Related Factor ◽  
Protective Effects

Kaempferol has been shown to protect cells against cerebral ischemia/reperfusion injury through inhibition of apoptosis. In the present study, we sought to investigate whether ferroptosis is involved in the oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal injury and the effects of kaempferol on ferroptosis in OGD/R-treated neurons. Western blot, immunofluorescence, and transmission electron microscopy were used to analyze ferroptosis, whereas cell death was detected using lactate dehydrogenase (LDH) release. We found that OGD/R attenuated SLC7A11 and glutathione peroxidase 4 (GPX4) levels as well as decreased endogenous antioxidants including nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), and superoxide dismutase (SOD) in neurons. Notably, OGD/R enhanced the accumulation of lipid peroxidation, leading to the induction of ferroptosis in neurons. However, kaempferol activated nuclear factor-E2-related factor 2 (Nrf2)/SLC7A11/GPX4 signaling, augmented antioxidant capacity, and suppressed the accumulation of lipid peroxidation in OGD/R-treated neurons. Furthermore, kaempferol significantly reversed OGD/R-induced ferroptosis. Nevertheless, inhibition of Nrf2 by ML385 blocked the protective effects of kaempferol on antioxidant capacity, lipid peroxidation, and ferroptosis in OGD/R-treated neurons. These results suggest that ferroptosis may be a significant cause of cell death associated with OGD/R. Kaempferol provides protection from OGD/R-induced ferroptosis partly by activating Nrf2/SLC7A11/GPX4 signaling pathway.

scholarly journals Autophagy impairment as a key feature for acetaminophen-induced ototoxicity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tong Zhao ◽  
Tihua Zheng ◽  
Huining Yu ◽  
Bo Hua Hu ◽  
Bing Hu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Lysosomal Enzymes ◽  
Apoptotic Cell ◽  
Cell Damage ◽  
Treatment Strategies ◽  
Explant Culture ◽  
Apoptotic Cell Death ◽  
Lysosomal Dysfunction ◽  
Autophagic Degradation

AbstractMacroautophagy/autophagy is a highly conserved self-digestion pathway that plays an important role in cytoprotection under stress conditions. Autophagy is involved in hepatotoxicity induced by acetaminophen (APAP) in experimental animals and in humans. APAP also causes ototoxicity. However, the role of autophagy in APAP-induced auditory hair cell damage is unclear. In the present study, we investigated autophagy mechanisms during APAP-induced cell death in a mouse auditory cell line (HEI-OC1) and mouse cochlear explant culture. We found that the expression of LC3-II protein and autophagic structures was increased in APAP-treated HEI-OC1 cells; however, the degradation of SQSTM1/p62 protein, the yellow puncta of mRFP-GFP-LC3 fluorescence, and the activity of lysosomal enzymes decreased in APAP-treated HEI-OC1 cells. The degradation of p62 protein and the expression of lysosomal enzymes also decreased in APAP-treated mouse cochlear explants. These data indicate that APAP treatment compromises autophagic degradation and causes lysosomal dysfunction. We suggest that lysosomal dysfunction may be directly responsible for APAP-induced autophagy impairment. Treatment with antioxidant N-acetylcysteine (NAC) partially alleviated APAP-induced autophagy impairment and apoptotic cell death, suggesting the involvement of oxidative stress in APAP-induced autophagy impairment. Inhibition of autophagy by knocking down of Atg5 and Atg7 aggravated APAP-induced ER and oxidative stress and increased apoptotic cell death. This study provides a better understanding of the mechanism responsible for APAP ototoxicity, which is important for future exploration of treatment strategies for the prevention of hearing loss caused by ototoxic medications.

scholarly journals High-density lipoprotein protects cardiomyocytes against necrosis induced by oxygen and glucose deprivation through SR-B1, PI3K, and AKT1 and 2

2018 ◽  
Vol 475 (7) ◽  
pp. 1253-1265 ◽  
Author(s):  
Kristina K. Durham ◽  
Kevin M. Chathely ◽  
Bernardo L. Trigatti
Keyword(s):  
Cell Death ◽  
High Density Lipoprotein ◽  
Ischemia Reperfusion ◽  
Density Lipoprotein ◽  
Glucose Deprivation ◽  
High Density ◽  
Dependent Manner ◽  
Protective Effects ◽  
Oxygen And Glucose Deprivation ◽  
Ventricular Cardiomyocytes

The cardioprotective lipoprotein HDL (high-density lipoprotein) prevents myocardial infarction and cardiomyocyte death due to ischemia/reperfusion injury. The scavenger receptor class B, type 1 (SR-B1) is a high-affinity HDL receptor and has been shown to mediate HDL-dependent lipid transport as well as signaling in a variety of different cell types. The contribution of SR-B1 in cardiomyocytes to the protective effects of HDL on cardiomyocyte survival following ischemia has not yet been studied. Here, we use a model of simulated ischemia (oxygen and glucose deprivation, OGD) to assess the mechanistic involvement of SR-B1, PI3K (phosphatidylinositol-3-kinase), and AKT in HDL-mediated protection of cardiomyocytes from cell death. Neonatal mouse cardiomyocytes and immortalized human ventricular cardiomyocytes, subjected to OGD for 4 h, underwent substantial cell death due to necrosis but not necroptosis or apoptosis. Pretreatment of cells with HDL, but not low-density lipoprotein, protected them against OGD-induced necrosis. HDL-mediated protection was lost in cardiomyocytes from SR-B1−/− mice or when SR-B1 was knocked down in human immortalized ventricular cardiomyocytes. HDL treatment induced the phosphorylation of AKT in cardiomyocytes in an SR-B1-dependent manner. Finally, chemical inhibition of PI3K or AKT or silencing of either AKT1 or AKT2 gene expression abolished HDL-mediated protection against OGD-induced necrosis of cardiomyocytes. These results are the first to identify a role of SR-B1 in mediating the protective effects of HDL against necrosis in cardiomyocytes, and to identify AKT activation downstream of SR-B1 in cardiomyocytes.

scholarly journals Neuroprotective Effects of Tetrahydrocurcumin against Glutamate-Induced Oxidative Stress in Hippocampal HT22 Cells

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 144 ◽  
Author(s):  
Chang-Hyun Park ◽  
Ji Hoon Song ◽  
Su-Nam Kim ◽  
Ji Hwan Lee ◽  
Hae-Jeung Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Protein Kinases ◽  
Apoptotic Cell ◽  
Curcuma Longa ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ht22 Cells ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

In the central nervous system, glutamate is a major excitable neurotransmitter responsible for many cellular functions. However, excessive levels of glutamate induce neuronal cell death via oxidative stress during acute brain injuries as well as chronic neurodegenerative diseases. The present study was conducted to examine the effect of tetrahydrocurcumin (THC), a major secondary metabolite of curcumin, and its possible mechanism against glutamate-induced cell death. We prepared THC using curcumin isolated from Curcuma longa (turmeric) and demonstrated the protective effect of THC against glutamate-induced oxidative stress in HT22 cells. THC abrogated glutamate-induced HT22 cell death and showed a strong antioxidant effect. THC also significantly reduced intracellular calcium ion increased by glutamate. Additionally, THC significantly reduced the accumulation of intracellular oxidative stress induced by glutamate. Furthermore, THC significantly diminished apoptotic cell death indicated by annexin V-positive in HT22 cells. Western blot analysis indicated that the phosphorylation of mitogen-activated protein kinases including c-Jun N-terminal kinase, extracellular signal-related kinases 1/2, and p38 by glutamate was significantly diminished by treatment with THC. In conclusion, THC is a potent neuroprotectant against glutamate-induced neuronal cell death by inhibiting the accumulation of oxidative stress and phosphorylation of mitogen-activated protein kinases.

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