The protective effect of metformin on mitochondrial dysfunction and endoplasmic reticulum stress in diabetic mice brain

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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Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

International Journal of Molecular Sciences ◽

10.3390/ijms22094646 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4646

Author(s):

Alexey A. Tinkov ◽

Monica M. B. Paoliello ◽

Aksana N. Mazilina ◽

Anatoly V. Skalny ◽

Airton C. Martins ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Mitochondrial Dysfunction ◽

Synaptic Dysfunction ◽

Future Research ◽

Protective Mechanism ◽

Autophagic Flux ◽

Future Research Directions ◽

The Impact

Understanding of the immediate mechanisms of Mn-induced neurotoxicity is rapidly evolving. We seek to provide a summary of recent findings in the field, with an emphasis to clarify existing gaps and future research directions. We provide, here, a brief review of pertinent discoveries related to Mn-induced neurotoxicity research from the last five years. Significant progress was achieved in understanding the role of Mn transporters, such as SLC39A14, SLC39A8, and SLC30A10, in the regulation of systemic and brain manganese handling. Genetic analysis identified multiple metabolic pathways that could be considered as Mn neurotoxicity targets, including oxidative stress, endoplasmic reticulum stress, apoptosis, neuroinflammation, cell signaling pathways, and interference with neurotransmitter metabolism, to name a few. Recent findings have also demonstrated the impact of Mn exposure on transcriptional regulation of these pathways. There is a significant role of autophagy as a protective mechanism against cytotoxic Mn neurotoxicity, yet also a role for Mn to induce autophagic flux itself and autophagic dysfunction under conditions of decreased Mn bioavailability. This ambivalent role may be at the crossroad of mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis. Yet very recent evidence suggests Mn can have toxic impacts below the no observed adverse effect of Mn-induced mitochondrial dysfunction. The impact of Mn exposure on supramolecular complexes SNARE and NLRP3 inflammasome greatly contributes to Mn-induced synaptic dysfunction and neuroinflammation, respectively. The aforementioned effects might be at least partially mediated by the impact of Mn on α-synuclein accumulation. In addition to Mn-induced synaptic dysfunction, impaired neurotransmission is shown to be mediated by the effects of Mn on neurotransmitter systems and their complex interplay. Although multiple novel mechanisms have been highlighted, additional studies are required to identify the critical targets of Mn-induced neurotoxicity.

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Protective effect of butanol extracts of skin of Anguilla japonica against endoplasmic reticulum stress-induced insulin resistance via the AMPK pathway in L6 myotubes

Food Science and Biotechnology ◽

10.1007/s10068-015-0137-5 ◽

2015 ◽

Vol 24 (3) ◽

pp. 1069-1075

Author(s):

Min Kyun Na ◽

Yong-Tae Jeong ◽

Xian Li ◽

Fansi Jin ◽

Seung-Lark Hwang ◽

...

Keyword(s):

Insulin Resistance ◽

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Protective Effect ◽

Anguilla Japonica ◽

Ampk Pathway ◽

L6 Myotubes

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Catechin-7-O-xyloside induces apoptosis via endoplasmic reticulum stress and mitochondrial dysfunction in human non-small cell lung carcinoma H1299 cells

Oncology Reports ◽

10.3892/or.2013.2840 ◽

2013 ◽

Vol 31 (1) ◽

pp. 314-320 ◽

Cited By ~ 3

Author(s):

JANG WON YOON ◽

JONG SUK LEE ◽

BYEONG MO KIM ◽

JOUNGJWA AHN ◽

KYUNG MI YANG

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Mitochondrial Dysfunction ◽

Lung Carcinoma ◽

Small Cell Lung Carcinoma ◽

Small Cell ◽

Small Cell Lung ◽

Cell Lung Carcinoma

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The impact of obesity on oocytes: evidence for lipotoxicity mechanisms

Reproduction Fertility and Development ◽

10.1071/rd11904 ◽

2012 ◽

Vol 24 (1) ◽

pp. 29 ◽

Cited By ~ 31

Author(s):

Linda L.-Y. Wu ◽

Robert J. Norman ◽

Rebecca L. Robker

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Mitochondrial Dysfunction ◽

Intracytoplasmic Sperm Injection ◽

Oocyte Quality ◽

Early Embryo ◽

Pregnancy Rates ◽

Clinical Literature ◽

The Impact

Obesity can have detrimental effects on pregnancy rates in natural conceptions and also in women undergoing IVF or intracytoplasmic sperm injection (ICSI). This review summarises the most recent clinical literature investigating whether obesity impacts oocyte quality and early embryo growth. In other tissues, obesity leads to lipotoxicity responses including endoplasmic reticulum stress, mitochondrial dysfunction and apoptosis. Recent reports indicate that lipotoxicity is a mechanism by which obesity may impact oocyte quality.

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