Silica nanoparticles mediated neuronal cell death in corpus striatum of rat brain: implication of mitochondrial, endoplasmic reticulum and oxidative stress

Parveen, Arshiya; Rizvi, Syed Husain Mustafa; Mahdi, Farzana; Tripathi, Sandeep; Ahmad, Iqbal; Shukla, Rohit; Khanna, Vinay K.; Singh, Ranjana; Patel, Devendra Kumar; Mahdi, Abbas Ali

doi:10.1007/s11051-014-2664-z

Cited by 27 publications

(19 citation statements)

References 58 publications

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“…CHOP/GADD153, sensor of endoplasmic reticulum stress, is highly up-regulated during ER stress [18,19]. In our studies, caspase 12 activation was observed to be associated with enhanced intracellular calcium levels together with increased mRNA and protein levels of CHOP/GADD153 [20,21]. CHOP is known to inhibit the expression of antiapoptotic Bcl 2 family proteins and disturbs the ratio of Bax/Bcl 2 [22,23].…”

Section: Er Stress and Apoptotic Signalingmentioning

confidence: 80%

Role of Endoplasmic Reticulum Stress and Unfolded Protein Responses in Health and Diseases

2015

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Endoplasmic reticulum (ER) is the site of protein synthesis, protein folding, maintainance of calcium homeostasis, synthesis of lipids and sterols. Genetic or environmental insults can alter its function generating ER stress. ER senses stress mainly by three stress sensor pathways, namely protein kinase R-like endoplasmic reticulum kinase-eukaryotic translation-initiation factor 2a, inositol-requiring enzyme 1a-X-box-binding protein 1 and activating transcription factor 6-CREBH, which induce unfolded protein responses (UPR) after the recognition of stress. Recent studies have demonstrated that ER stress and UPR signaling are involved in cancer, metabolic disorders, inflammatory diseases, osteoporosis and neurodegenerative diseases. However, the precise knowledge regarding involvement of ER stress in different disease processes is still debatable. Here we discuss the possible role of ER stress in various disorders on the basis of existing literature. An attempt has also been made to highlight the present knowledge of this field which may help to elucidate and conjure basic mechanisms and novel insights into disease processes which could assist in devising better future diagnostic and therapeutic strategies.

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Section: Er Stress and Apoptotic Signalingmentioning

confidence: 80%

Role of Endoplasmic Reticulum Stress and Unfolded Protein Responses in Health and Diseases

2015

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“…Molecular mechanisms activated in response to NP treatment are strictly dependent on the cellular uptake of these particles, and it is increasingly recognized that SiNPs can easily enter cells by endocytosis, localizing to the cytoplasm or crucial cellular organelles, such as the ER 46 and mitochondria. 14 Indeed, SiNPs have been shown to interfere with the ER, affecting homeostasis and causing a state known as ER stress.…”

Section: Discussionmentioning

confidence: 99%

“…14 Indeed, SiNPs have been shown to interfere with the ER, affecting homeostasis and causing a state known as ER stress. 5,6,46 Downstream of ER stress, the unfolded protein response is initiated, with one of two potential outcomes: activation of prosurvival pathways via increased expression of chaperone proteins GRP78, GRP94, and ORP150, or activation of a proapoptotic pathway through enhanced expression of CHOP. 15,16 Therefore, increased levels of ER chaperones and CHOP are considered markers of ER stress.…”

Section: Discussionmentioning

confidence: 99%

Silica nanoparticle-induced oxidative stress and mitochondrial damage is followed by activation of intrinsic apoptosis pathway in glioblastoma cells

Kusaczuk¹,

Krętowski²,

Naumowicz³

et al. 2018

IJN

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IntroductionRecently, the focus of oncological research has been on the optimization of therapeutic strategies targeted at malignant diseases. Nanomedicine utilizing silicon dioxide nanoparticles (SiNPs) is one such strategy and is rapidly developing as a promising tool for cancer diagnosis, imaging, and treatment. Nevertheless, little is known about the mechanisms of action of SiNPs in brain tumors.Materials and methodsHere, we explored the effects of 5–15 nm SiNPs in the human glioblastoma cell line LN229. In this respect, MTT assays, microscopic observations, flow cytometry analyses, and luminescent assays were performed. Moreover, RT-qPCR and Western blot analyses were done to determine gene and protein expressions.ResultsWe demonstrated that SiNPs triggered evident cytotoxicity, with microscopic observations of the nuclei, annexin V–fluorescein isothiocyanate/propidium iodide staining, and elevated caspase 3/7 activity, suggesting that SiNPs predominantly induced apoptotic death in LN229 cells. We further showed the occurrence of oxidative stress induced by enhanced reactive oxygen-species generation. This effect was followed by deregulated expression of genes encoding the antioxidant enzymes SOD1, SOD2, and CAT, and impaired mitochondria function. SiNP- induced mitochondrial dysfunction was characterized by membrane-potential collapse, ATP depletion, elevated expression of BAX, PUMA, and NOXA with simultaneous downregulation of BCL2/BCL2L1, and activation of caspase 9. Moreover, RT-qPCR and Western blot analyses demonstrated increased levels of the endoplasmic reticulum stress markers GRP78, GRP94, and DDIT3, as well as strongly increased expressions of the IL1B and COX2 genes, suggesting activation of endoplasmic reticulum stress and a proinflammatory response.ConclusionsAltogether, our data indicate that in LN229 cells, SiNPs evoke cell death via activation of the intrinsic apoptosis pathway and suggest that other aspects of cellular function may also be affected. As such, SiNPs represent a potentially promising agent for facilitating further progress in brain cancer therapy. However, further exploration of SiNP long-term toxicity and molecular effects is necessary prior to their widespread application.

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“…En general, los nanomateriales después de depositarse dentro del cuerpo no son degradados fácilmente y pueden retenerse incluso por varios meses causando alteraciones dentro de las células donde se hayan depositado. Tal es el caso de las nanopartículas de plata y de dióxido de silicio que se acumulan en el cerebro de ratas durante 12 semanas de exposición (Parveen et al, 2014;Wen et al, 2015), además, causan apoptosis y disminución de la viabilidad celular (Hsiao et al, 2017), así como alteraciones de la morfología celular y producción de especies reactivas de oxígeno, respectivamente (Yang et al, 2014). Es por ello que ha surgido la preocupación de si los neuronanomateriales podrían causar neurotoxicidad después de ejercer su efecto, por caso, después de liberar un fármaco, debido a la baja capacidad para ser eliminados del sistema nervioso.…”

Section: Desventajasunclassified

“…Por su parte, las nanopartículas de dióxido de silicio también pueden cruzar la barrera hematoencefálica y depositarse en diferentes zonas del cerebro, como en el cuerpo estriado (Parveen et al, 2014), el hipocampo, entre otras (Wu et al, 2011). Estas nanopartículas disminuyen la defensa antioxi-dante, aumentan la cantidad de ros y promueven la liberación de citocinas proinflamatorias.…”

Section: Estudios De Toxicidad De Nanomateriales En El Sncunclassified

¿Los nanomateriales pueden causar neurotoxicidad?

Jiménez-Barrios

Chirino

2018

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La nanotecnología se centra en el uso de nanomateriales manufacturados que se emplean en el área médica, robótica, electrónica, mecánica y alimenticia, entre muchas otras. Dichos nanomateriales están compuestos de nanopartículas que tienen un tamaño de 1 a 100 nm de diámetro. Debido a dicho tamaño, si se inhalan, por ejemplo en las industrias en donde se manufacturan o procesan, pueden depositarse en el tracto respiratorio y translocarse a torrente sanguíneo y posteriormente ser depositados en diferentes tejidos. Algunos alimentos o empaques que contienen nanopartículas también pueden ser una fuente de exposición y por vía oral, también pueden alcanzar torrente sanguíneo, lo cual genera la preocupación de que puedan cruzar la barrera hematoencefálica y ser depositadas en cerebro. Existen además algunos nanomateriales que se usan en aplicaciones biomédicas para liberar fármacos directamente en cerebro o generar imágenes para determinar si hay lesiones asociadas a traumas o enfermedades. Otra de las preocupaciones es que muchas nanopartículas no se degradan, por lo que se desconoce cuánto tiempo podrían permanecer en los tejidos en donde se internalizan. Específicamente, si las nanopartículas llegan a cerebro pueden causar alteraciones en diferentes zonas que afectarían funciones motoras, la memoria, el aprendizaje, entre otras. Además, debido a que una vez que se depositan en un tejido causan inflamación entre otras alteraciones, podrían también promover procesos patológicos o exacerbar enfermedades neurodegenerativas. En este artículo, explicamos a) qué son los nanomateriales, b) cómo estamos expuestos a ellos, c) cuáles son sus aplicaciones, d) cómo podrían causar daño si se depositan en cerebro, y e) cuáles son las evidencias que sustentan que podrían causar daño. Finalmente sugerimos algunas consideraciones para el diseño y estudio de los efectos de nanomateriales en sistema nervioso central.

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Silica nanoparticles mediated neuronal cell death in corpus striatum of rat brain: implication of mitochondrial, endoplasmic reticulum and oxidative stress

Cited by 27 publications

References 58 publications

Role of Endoplasmic Reticulum Stress and Unfolded Protein Responses in Health and Diseases

Role of Endoplasmic Reticulum Stress and Unfolded Protein Responses in Health and Diseases

Silica nanoparticle-induced oxidative stress and mitochondrial damage is followed by activation of intrinsic apoptosis pathway in glioblastoma cells

¿Los nanomateriales pueden causar neurotoxicidad?

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