scholarly journals Copper as a Collaborative Partner of Zinc-Induced Neurotoxicity in the Pathogenesis of Vascular Dementia

2021 ◽  
Vol 22 (14) ◽  
pp. 7242
Author(s):  
Masahiro Kawahara ◽  
Ken-ichiro Tanaka ◽  
Midori Kato-Negishi
Keyword(s):  
Vascular Dementia ◽  
Oxygen Species ◽  
Jnk Signaling ◽  
Amino Terminal ◽  
Brain Functions ◽  
Jnk Signaling Pathway ◽  
Neuronal Transmission ◽  
Transient Global Ischemia ◽  
Stress Pathway ◽  
Excess Zinc

Copper is an essential trace element and possesses critical roles in various brain functions. A considerable amount of copper accumulates in the synapse and is secreted in neuronal firings in a manner similar to zinc. Synaptic copper and zinc modulate neuronal transmission and contribute to information processing. It has been established that excess zinc secreted during transient global ischemia plays central roles in ischemia-induced neuronal death and the pathogenesis of vascular dementia. We found that a low concentration of copper exacerbates zinc-induced neurotoxicity, and we have demonstrated the involvement of the endoplasmic reticulum (ER) stress pathway, the stress-activated protein kinases/c-Jun amino-terminal kinases (SAPK/JNK) signaling pathway, and copper-induced reactive oxygen species (ROS) production. On the basis of our results and other studies, we discuss the collaborative roles of copper in zinc-induced neurotoxicity in the synapse and the contribution of copper to the pathogenesis of vascular dementia.

scholarly journals Carnosine as a Possible Drug for Zinc-Induced Neurotoxicity and Vascular Dementia

2020 ◽  
Vol 21 (7) ◽  
pp. 2570 ◽  
Author(s):  
Masahiro Kawahara ◽  
Yutaka Sadakane ◽  
Keiko Mizuno ◽  
Midori Kato-Negishi ◽  
Ken-ichiro Tanaka
Keyword(s):  
Vascular Dementia ◽  
Dementia With Lewy Bodies ◽  
Energy Production ◽  
Therapeutic Agent ◽  
Lewy Bodies ◽  
Agricultural Products ◽  
Oxygen Species ◽  
Jnk Pathway ◽  
Amino Terminal ◽  
Stress Pathway

Increasing evidence suggests that the metal homeostasis is involved in the pathogenesis of various neurodegenerative diseases including senile type of dementia such as Alzheimer’s disease, dementia with Lewy bodies, and vascular dementia. In particular, synaptic Zn2+ is known to play critical roles in the pathogenesis of vascular dementia. In this article, we review the molecular pathways of Zn2+-induced neurotoxicity based on our and numerous other findings, and demonstrated the implications of the energy production pathway, the disruption of calcium homeostasis, the production of reactive oxygen species (ROS), the endoplasmic reticulum (ER)-stress pathway, and the stress-activated protein kinases/c-Jun amino-terminal kinases (SAPK/JNK) pathway. Furthermore, we have searched for substances that protect neurons from Zn2+-induced neurotoxicity among various agricultural products and determined carnosine (β-alanyl histidine) as a possible therapeutic agent for vascular dementia.

scholarly journals The Drosophila Shark tyrosine kinase is required for embryonic dorsal closure

2000 ◽  
Vol 14 (5) ◽  
pp. 604-614
Author(s):  
Rafael Fernandez ◽  
Fumitaka Takahashi ◽  
Zhao Liu ◽  
Ruth Steward ◽  
David Stein ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Leading Edge ◽  
Dorsal Closure ◽  
Kinase Gene ◽  
Dorsal Midline ◽  
Jnk Signaling ◽  
Amino Terminal ◽  
Tyrosine Kinase Gene ◽  
Epithelial Sheet ◽  
Jnk Signaling Pathway

Dorsal closure (DC) in the Drosophila embryo requires the coordinated interaction of two different functional domains of the epidermal cell layer—the leading edge (LE) and the lateral epidermis. In response to activation of a conserved c-Jun amino-terminal kinase (JNK) signaling module, the dorsal-most layer of cells, which constitute the LE of the stretching epithelial sheet, secrete Dpp, a member of the TGFβ superfamily. Dpp and other LE cell-derived signaling molecules stimulate the bilateral dorsal elongation of cells of the dorsolateral epidermis over the underlaying amnioserosa and the eventual fusion of their LEs along the dorsal midline. We have found that flies bearing a Shark tyrosine kinase gene mutation,shark1, exhibit a DC-defective phenotype. Dpp fails to be expressed in shark1 mutant LE cells. Consistent with these observations, epidermal-specific reconstitution ofshark function or overexpression of an activated form of c-Jun in the shark1 mutant background, rescues the DC defect. Thus, Shark regulates the JNK signaling pathway leading to Dpp expression in LE cells. Furthermore, constitutive activation of the Dpp pathway throughout the epidermis fails to rescue theshark1 DC defect, suggesting that Shark may function in additional pathways in the LE and/or lateral epithelium.

scholarly journals TAK1 Participates in c-Jun N-Terminal Kinase Signaling during Drosophila Development

2000 ◽  
Vol 20 (9) ◽  
pp. 3015-3026 ◽  
Author(s):  
Yoshihiro Takatsu ◽  
Makoto Nakamura ◽  
Mark Stapleton ◽  
Maria C. Danos ◽  
Kunihiro Matsumoto ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Cultured Cells ◽  
Transforming Growth Factor Β ◽  
Kinase Domain ◽  
Dominant Negative ◽  
Jnk Signaling ◽  
Amino Terminal ◽  
Jnk Signaling Pathway

ABSTRACT Transforming growth factor β (TGF-β)-activated kinase 1 (TAK1) is a member of the MAPKKK superfamily and has been characterized as a component of the TGF-β/bone morphogenetic protein signaling pathway. TAK1 function has been extensively studied in cultured cells, but its in vivo function is not fully understood. In this study, we isolated aDrosophila homolog of TAK1 (dTAK1) which contains an extensively conserved NH2-terminal kinase domain and a partially conserved COOH-terminal domain. To learn about possible endogenous roles of TAK1 during animal development, we generated transgenic flies which express dTAK1 or the mouseTAK1 (mTAK1) gene in the fly visual system. Ectopic activation of TAK1 signaling leads to a small eye phenotype, and genetic analysis reveals that this phenotype is a result of ectopically induced apoptosis. Genetic and biochemical analyses also indicate that the c-Jun amino-terminal kinase (JNK) signaling pathway is specifically activated by TAK1 signaling. Expression of a dominant negative form of dTAK during embryonic development resulted in various embryonic cuticle defects including dorsal open phenotypes. Our results strongly suggest that in Drosophila melanogaster, TAK1 functions as a MAPKKK in the JNK signaling pathway and participates in such diverse roles as control of cell shape and regulation of apoptosis.

scholarly journals The Hypothetical Inclusion Membrane Protein CPSIT_0846 Regulates Mitochondrial-Mediated Host Cell Apoptosis via the ERK/JNK Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Ting Tang ◽  
Haiying Wu ◽  
Xi Chen ◽  
Li Chen ◽  
Luyao Liu ◽  
...  
Keyword(s):  
Host Cell ◽  
Signaling Pathway ◽  
Hela Cells ◽  
Cell Apoptosis ◽  
B Cell Lymphoma ◽  
Inclusion Membrane ◽  
Jnk Signaling ◽  
Amino Terminal ◽  
Host Cell Apoptosis ◽  
Jnk Signaling Pathway

Chlamydia psittaci is an important zoonotic factor associated with human and animal atypical pneumonia. Resisting host cell apoptosis is central to sustaining Chlamydia infection in vivo. Chlamydia can secrete inclusion membrane proteins (Incs) that play important roles in their development cycle and pathogenesis. CPSIT_0846 is an Inc protein in C. psittaci identified by our team in previous work. In the current study, we investigated the regulatory role of CPSIT_0846 in HeLa cell apoptosis, and explored potential mechanisms. The results showed that HeLa cells treated with CPSIT_0846 contained fewer apoptotic bodies and exhibited a lower apoptotic rate than untreated cells either with Hoechst 33258 fluorescence staining or flow cytometry with or without induction by staurosporine (STS). CPSIT_0846 could increase the phosphorylation of the extracellular signal-regulated kinases 1/2 (ERK1/2) or stress-activated protein kinases/c-Jun amino-terminal kinases (SAPK/JNK) signaling pathways, and the Bcl-2 associated X protein (Bax)/B cell lymphoma 2 (Bcl-2) ratio, levels of cleaved caspase-3/9 and cleaved Poly-ADP-ribose polymerase (PARP) were significantly up-regulated following inhibition of ERK1/2 or SAPK/JNK pathways with U0126 or SP600125. After carbonyl cyanide 3-chlorophenylhydrazone (CCCP) treatment, the mitochondrial membrane potential (MMP) of cells was significantly decreased in control group, but stable in the CPSIT_0846 treated one, and less cytochrome c (Cyt.c) was released into the cytoplasm. Inhibition of the ERK1/2 or SAPK/JNK pathway significantly decreased the JC-1 red-green fluorescence signal, and promoted Cyt.c discharge into the cytoplasm in HeLa cells treated with CPSIT_0846. In conclusion, CPSIT_0846 can regulate mitochondrial pathway-mediated apoptosis in HeLa cells by activating the ERK/JNK signaling pathway.

scholarly journals Ciclopirox induces autophagy through reactive oxygen species-mediated activation of JNK signaling pathway

Oncotarget ◽  
2014 ◽  
Vol 5 (20) ◽  
pp. 10140-10150 ◽  
Author(s):  
Hongyu Zhou ◽  
Tao Shen ◽  
Chaowei Shang ◽  
Yan Luo ◽  
Lei Liu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Signaling Pathway ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway

scholarly journals Electroacupuncture inhibits hippocampal neuronal apoptosis and improves cognitive dysfunction in mice with vascular dementia via modulating JNK signaling pathway

2021 ◽  
Author(s):  
Yaru Liu ◽  
Chunyan Li ◽  
Zhenyang Yan ◽  
Yafei Ren ◽  
Woyu Wang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Vascular Dementia ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Neuroprotective Effects ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway ◽  
Dependent Pathway

Abstract Background: Nerve cell apoptosis is an important pathological mechanism of vascular dementia (VaD). There are evidences that Electroacupuncture (EA) can reduce cognitive impairment in VaD patients and protect nerve cells. However, the mechanism remains unknown. JNK signaling pathway play an important role in apoptosis. And JNK induces cell apoptosis in two main ways, namely JNK transcription-dependent pathway and JNK transcription-independent route. We focus on whether EA can inhibit apoptosis and alleviate cognitive impairment by regulating JNK signaling pathway.Method: In this study, Bilateral common carotid artery clipping (BCCAo) was used as a method to establish VaD mouse model. Longa scoring method and Morris water maze were used to evaluate whether EA could improve the behavioral score of VaD mice. The neuroprotective effects of EA were evaluated by the Hematoxylin and Eosin (HE) staining, TUNEL and Flow Cytometry (FCM). Western blot and real-time PCR were used to detect the expression of JNK-3, AP-1, P53, Bcl -2, Bax, and Caspase-3.Results: Our findings indicated that EA could improve the behavioral scores of VaD mice. VaD mice treated with EA reduced hippocampal neuronal apoptosis. In addition, EA could reduce the expression of JNK-3, AP-1, P53, Bax and Caspase-3 proteins and mRNA in the hippocampus of VaD mice, and increase the expression of Bcl-2.Conclusion: Our findings suggested that the mechanism of action of EA to treat VaD may be related to its regulation of JNK transcription-dependent pathway and JNK transcription-independent route.

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