Tanshinone IIA exerts neuroprotective effects on hippocampus-dependent cognitive impairments in diabetic rats by attenuating ER stress-induced apoptosis

Background and Objective: This study investigated whether rapamycin has a protective effect on the testis of diabetic rats by regulating autophagy, endoplasmic reticulum stress, and oxidative stress. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups: control, diabetic, and diabetic treated with rapamycin, which received gavage of rapamycin (2mg.kg-1.d-1) after induction of diabetes. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 65mg.Kg-1). All rats were sacrificed at the termination after 8 weeks of rapamycin treatment. The testicular pathological changes were determined by hematoxylin and eosin staining. The protein or mRNA expression of autophagy-related proteins (Beclin1, microtubule-associated protein light chain 3 (LC3), p62), ER stress marked proteins (CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), caspase-12), oxidative stress-related proteins (p22phox, nuclear factor erythroid2-related factor 2 (Nrf2)) and apoptosis-related proteins (Bax, B cell lymphoma-2 (Bcl-2)) were assayed by western blot or real-time fluorescence quantitative PCR. Results: There were significant pathological changes in the testes of diabetic rats. The expression of Beclin1, LC3, Nrf2, Bcl-2 were significantly decreased and p62, CHOP, caspase12, p22phox, and Bax were notably increased in the testis of diabetic rats (P <0.05). However, rapamycin treatment for 8 weeks significantly reversed the above changes in the testis of diabetic rats (P <0.05). Conclusion: Rapamycin appears to produce a protective effect on the testes of diabetic rats by inducing the expression of autophagy and inhibiting the expression of ER-stress, oxidative stress, and apoptosis.

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5-ALA Attenuates the Palmitic Acid-Induced ER Stress and Apoptosis in Bovine Mammary Epithelial Cells

Molecules ◽

10.3390/molecules26041183 ◽

2021 ◽

Vol 26 (4) ◽

pp. 1183

Author(s):

Mst Mamuna Sharmin ◽

Md Aminul Islam ◽

Itsuki Yamamoto ◽

Shin Taniguchi ◽

Shinichi Yonekura

Keyword(s):

T Cells ◽

Epithelial Cells ◽

Palmitic Acid ◽

Er Stress ◽

Aminolevulinic Acid ◽

Mammary Epithelial Cells ◽

Mammary Epithelial ◽

Protective Effects ◽

Bovine Mammary Epithelial Cells ◽

Induced Apoptosis

The conservation of mammary gland physiology by maintaining the maximum number of mammary epithelial cells (MECs) is of the utmost importance for the optimum amount of milk production. In a state of negative energy balance, palmitic acid (PA) reduces the number of bovine MECs. However, there is no effective strategy against PA-induced apoptosis of MECs. In the present study, 5-aminolevulinic acid (5-ALA) was established as a remedial agent against PA-induced apoptosis of MAC-T cells (an established line of bovine MECs). In PA-treated cells, the apoptosis-related genes BCL2 and BAX were down- and upregulated, respectively. The elevated expression of major genes of the unfolded protein response (UPR), such as CHOP, a proapoptotic marker (C/EBP homologous protein), reduced the viability of PA-treated MAC-T cells. In contrast, 5-ALA pretreatment increased and decreased BCL2 and BAX expression, respectively. Moreover, cleaved caspase-3 protein expression was significantly reduced in the 5-ALA-pretreated group in comparison with the PA group. The downregulation of major UPR-related genes, including CHOP, extended the viability of MAC-T cells pretreated with 5-ALA and also reduced the enhanced intensity of the PA-induced expression of phospho-protein kinase R-like ER kinase. Moreover, the enhanced expression of HO-1 (antioxidant gene heme oxygenase) by 5-ALA reduced PA-induced oxidative stress (OxS). HO-1 is not only protective against OxS but also effective against ER stress. Collectively, these findings offer new insights into the protective effects of 5-ALA against PA-induced apoptosis of bovine MECs.

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iPLA2β Contributes to ER Stress-Induced Apoptosis during Myocardial Ischemia/Reperfusion Injury

Cells ◽

10.3390/cells10061446 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1446

Author(s):

Tingting Jin ◽

Jun Lin ◽

Yingchao Gong ◽

Xukun Bi ◽

Shasha Hu ◽

...

Keyword(s):

Cell Death ◽

Heart Disease ◽

Myocardial Ischemia ◽

Ischemic Heart Disease ◽

Er Stress ◽

Ischemia Reperfusion ◽

Myocardial Ischemia Reperfusion ◽

Induced Apoptosis

Both calcium-independent phospholipase A2 beta (iPLA2β) and endoplasmic reticulum (ER) stress regulate important pathophysiological processes including inflammation, calcium homeostasis and apoptosis. However, their roles in ischemic heart disease are poorly understood. Here, we show that the expression of iPLA2β is increased during myocardial ischemia/reperfusion (I/R) injury, concomitant with the induction of ER stress and the upregulation of cell death. We further show that the levels of iPLA2β in serum collected from acute myocardial infarction (AMI) patients and in samples collected from both in vivo and in vitro I/R injury models are significantly elevated. Further, iPLA2β knockout mice and siRNA mediated iPLA2β knockdown are employed to evaluate the ER stress and cell apoptosis during I/R injury. Additionally, cell surface protein biotinylation and immunofluorescence assays are used to trace and locate iPLA2β. Our data demonstrate the increase of iPLA2β augments ER stress and enhances cardiomyocyte apoptosis during I/R injury in vitro and in vivo. Inhibition of iPLA2β ameliorates ER stress and decreases cell death. Mechanistically, iPLA2β promotes ER stress and apoptosis by translocating to ER upon myocardial I/R injury. Together, our study suggests iPLA2β contributes to ER stress-induced apoptosis during myocardial I/R injury, which may serve as a potential therapeutic target against ischemic heart disease.

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Characterization of Endoplasmic Reticulum (ER) in Human Pluripotent Stem Cells Revealed Increased Susceptibility to Cell Death upon ER Stress

Cells ◽

10.3390/cells9051078 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1078

Author(s):

Tae Won Ha ◽

Ji Hun Jeong ◽

HyeonSeok Shin ◽

Hyun Kyu Kim ◽

Jeong Suk Im ◽

...

Keyword(s):

Stem Cells ◽

Endoplasmic Reticulum ◽

Er Stress ◽

Pluripotent Stem Cells ◽

Meta Analysis ◽

Embryonic Stem ◽

Structural Features ◽

Human Pluripotent Stem Cells ◽

Differentiated Cells ◽

Induced Apoptosis

Human pluripotent stem cells (hPSCs), such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have a well-orchestrated program for differentiation and self-renewal. However, the structural features of unique proteostatic-maintaining mechanisms in hPSCs and their features, distinct from those of differentiated cells, in response to cellular stress remain unclear. We evaluated and compared the morphological features and stress response of hPSCs and fibroblasts. Compared to fibroblasts, electron microscopy showed simpler/fewer structures with fewer networks in the endoplasmic reticulum (ER) of hPSCs, as well as lower expression of ER-related genes according to meta-analysis. As hPSCs contain low levels of binding immunoglobulin protein (BiP), an ER chaperone, thapsigargin treatment sharply increased the gene expression of the unfolded protein response. Thus, hPSCs with decreased chaperone function reacted sensitively to ER stress and entered apoptosis faster than fibroblasts. Such ER stress-induced apoptotic processes were abolished by tauroursodeoxycholic acid, an ER-stress reliever. Hence, our results revealed that as PSCs have an underdeveloped structure and express fewer BiP chaperone proteins than somatic cells, they are more susceptible to ER stress-induced apoptosis in response to stress.

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Apoptosis Induced by Tanshinone IIA and Cryptotanshinone Is Mediated by Distinct JAK/STAT3/5 and SHP1/2 Signaling in Chronic Myeloid Leukemia K562 Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/805639 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 19

Author(s):

Ji Hoon Jung ◽

Tae-Rin Kwon ◽

Soo-Jin Jeong ◽

Eun-Ok Kim ◽

Eun Jung Sohn ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Biological Effects ◽

K562 Cells ◽

Tanshinone Iia ◽

Anticancer Activities ◽

Caspase 9 ◽

Anticancer Effects ◽

Induced Apoptosis ◽

Better Than

Though tanshinone IIA and cryptotanshinone possess a variety of biological effects such as anti-inflammatory, antioxidative, antimetabolic, and anticancer effects, the precise molecular targets or pathways responsible for anticancer activities of tanshinone IIA and cryptotanshinone in chronic myeloid leukemia (CML) still remain unclear. In the present study, we investigated the effect of tanshinone IIA and cryptotanshinone on the Janus activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling during apoptotic process. We found that both tanshinone IIA and cryptotanshinone induced apoptosis by activation of caspase-9/3 and Sub-G1 accumulation in K562 cells. However, they have the distinct JAK/STAT pathway, in which tanshinone IIA inhibits JAK2/STAT5 signaling, whereas cryptotanshinone targets the JAK2/STAT3. In addition, tanshinone IIA enhanced the expression of both SHP-1 and -2, while cryptotanshinone regulated the expression of only SHP-1. Both tanshinone IIA and cryptotanshinone attenuated the expression of bcl-xL, survivin, and cyclin D1. Furthermore, tanshinone IIA augmented synergy with imatinib, a CML chemotherapeutic drug, better than cryptotanshinone in K562 cells. Overall, our findings suggest that the anticancer activity of tanshinone IIA and cryptotanshinone is mediated by the distinct the JAK/STAT3/5 and SHP1/2 signaling, and tanshinone IIA has the potential for combination therapy with imatinib in K562 CML cells.

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Neuroprotective effects of nicotic receptor stimulation by ER stress and autophagy regulation

Neuroscience Research ◽

10.1016/j.neures.2009.09.555 ◽

2009 ◽

Vol 65 ◽

pp. S118

Author(s):

Hiroki Takeuchi ◽

Haruhisa Inoue ◽

Akinori Akaike ◽

Hideyuki Sawada ◽

Shun Shimohama ◽

...

Keyword(s):

Er Stress ◽

Receptor Stimulation ◽

Neuroprotective Effects

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Effect of feeding with bilberry fruit on the expression pattern of αCaMKII in hippocampal neurons in normal and diabetic rats

Polish Journal of Veterinary Sciences ◽

10.1515/pjvs-2017-0038 ◽

2017 ◽

Vol 20 (2) ◽

pp. 313-319 ◽

Cited By ~ 5

Author(s):

M. Matysek ◽

S. Mozel ◽

R. Szalak ◽

A. Zacharko-Siembida ◽

K. Obszańska ◽

...

Keyword(s):

Cognitive Processes ◽

Hippocampal Neurons ◽

Negative Impact ◽

Expression Patterns ◽

Memory Loss ◽

Diabetic Rats ◽

Control Group ◽

Neuroprotective Effects ◽

The Central Nervous System ◽

And Control

Abstract αCaMKII, widely occurring in the central nervous system, plays a significant role in cognitive processes. It is well known that diabetes is a risk factor that may trigger brain atrophy, cognitive dysfunction and finally lead to memory loss. Antioxidants richly present in bilberry fruits are believed to have significant effects on diabetes-related brain dysfunctions mainly due to their abilities to modulate neurotransmitter release that lead to reduction of the negative impact of free radicals on cognitive processes. The aim of the present research was to immunohistochemically investigate the expression patterns of αCaMKII in hippocampal neurons from non-diabetic, diabetic and diabetic rats fed with an extract of bilberry fruit. The obtained results show that in comparison to the control group, in diabetic rats hippocampal neurons immunoreactive (ir) to αCaMKII were swollen and the lengths of the neuronal fibres were reduced. Further study shows that in diabetic rats fed with bilberry fruit, αCaMKII-positive nerve fibres were significantly longer when compared to the groups of diabetic and control rats. Additionally, we observed statistically significant changes in the average larger diameter of αCaMKII-ir hippocampal neurons between groups of diabetic rats (with vs. without supplement of bilberry fruit). The results of the present work suggest that antioxidants present in bilberry fruits influence the morphology of and possibly exhibit beneficial and neuroprotective effects on hippocampal neurons during diabetes. It is likely that changes in the appearance of αCaMKII-expressed hippocampal neurons may reflect the diabetes-evoked rise in Ca2+ level in the cerebral nerve terminals. The present research extends our knowledge of preventive mechanisms for cognitive dysfunctions occurring in the brain during diabetes.

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