scholarly journals Thiazoline-related innate fear stimuli orchestrate hypothermia and anti-hypoxia via sensory TRPA1 activation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tomohiko Matsuo ◽  
Tomoko Isosaka ◽  
Yuichiro Hayashi ◽  
Lijun Tang ◽  
Akihiro Doi ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Hypoxic Condition ◽  
Olfactory Pathway ◽  
Sensory Pathways ◽  
Hypoxic Conditions ◽  
Transient Receptor ◽  
Artificial Activation ◽  
Innate Fear

AbstractThiazoline-related innate fear-eliciting compounds (tFOs) orchestrate hypothermia, hypometabolism, and anti-hypoxia, which enable survival in lethal hypoxic conditions. Here, we show that most of these effects are severely attenuated in transient receptor potential ankyrin 1 (Trpa1) knockout mice. TFO-induced hypothermia involves the Trpa1-mediated trigeminal/vagal pathways and non-Trpa1 olfactory pathway. TFOs activate Trpa1-positive sensory pathways projecting from trigeminal and vagal ganglia to the spinal trigeminal nucleus (Sp5) and nucleus of the solitary tract (NTS), and their artificial activation induces hypothermia. TFO presentation activates the NTS-Parabrachial nucleus pathway to induce hypothermia and hypometabolism; this activation was suppressed in Trpa1 knockout mice. TRPA1 activation is insufficient to trigger tFO-mediated anti-hypoxic effects; Sp5/NTS activation is also necessary. Accordingly, we find a novel molecule that enables mice to survive in a lethal hypoxic condition ten times longer than known tFOs. Combinations of appropriate tFOs and TRPA1 command intrinsic physiological responses relevant to survival fate.

scholarly journals Transient Receptor Potential Melastatin 2 Enhances Vascular Reactivity During Development of Atherosclerosis in Mice

2021 ◽  
Vol 34 (1) ◽  
pp. 121-122
Author(s):  
Yi-quan Dai ◽  
Xiao-xiao Yan ◽  
Yi-chen Lin ◽  
Hong-yu Chen ◽  
Xiao-ru Liu
Keyword(s):  
Knockout Mice ◽  
Vascular Reactivity ◽  
Transient Receptor Potential ◽  
Gene Knockout ◽  
Receptor Potential ◽  
Blood Lipid ◽  
Normal Diet ◽  
Protein Levels ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

Abstract Background To investigate the function of transient receptor potential melastatin 2 (TRPM2) in vascular reactivity induced by 5-hydroxytryptamine (5-HT) in the aorta during development of atherosclerosis in mice. Methods Forty mice were randomly divided into 4 groups: C57BL/6J on normal diet (C57 + ND), C57BL/6J on high-fat diet (C57 + HFD), apolipoprotein E gene knockout mice (ApoE−/−) on ND (ApoE−/− + ND), and ApoE−/− on HFD (ApoE−/− + HFD). They were fed with a ND or HFD for 16 weeks. Aortic TRPM2 expression and isometric contractions were analyzed. Results In the ApoE−/− + HFD group, body weight, blood glucose, and blood lipid concentrations were increased, and aortic plaques were developed. Compared with the other 3 groups, aortic TRPM2 mRNA and protein levels were significantly increased in the ApoE−/− + HFD group (P < 0.01). Aortic reactivity to 5-HT was enhanced in ApoE−/− + HFD mice with lower EC50 values. The enhanced reactivity to 5-HT was significantly inhibited by TRPM2 inhibitors, N-p-amylcinnamoyl anthranilic acid (1 µmol/l) and 2-aminoethyl diphenylborinate (10 µmol/l). Conclusions Aortic TRPM2 expression is upregulated in ApoE knockout mice fed with a HFD. Upregulation of TRPM2 enhances 5-HT vascular reactivity during development of atherosclerosis.

Examination of the demyelination process in mGFAP‐driven conditional transient receptor potential ankyrin 1 (TRPA1) receptor knockout mice

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Erika Pintér ◽  
Kata Böcskei ◽  
Gábor Kriszta ◽  
Zoltán Sándor ◽  
Balázs Nemes ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor

scholarly journals TRPC6-Mediated Ca2+ Signaling is Required for Hypoxia-Induced Autophagy in Human Podocytes

2018 ◽  
Vol 48 (4) ◽  
pp. 1782-1792 ◽  
Author(s):  
Tianrong Ji ◽  
Chengwei Zhang ◽  
Linlin Ma ◽  
Qin Wang ◽  
Li Zou ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Adenosine Monophosphate ◽  
Ampk Signaling ◽  
Hypoxic Conditions ◽  
Transient Receptor ◽  
Ca2 Channels

Background/Aims: Intracellular Ca2+ signaling plays an important role in the regulation of autophagy. However, very little is known about the role of Ca2+ influx, which is induced by plasma membrane Ca2+ channels. Our previous study showed that transient receptor potential canonical channel-6 (TRPC6), a major Ca2+ influx pathway in podocytes, was activated by hypoxia. Here, we investigated whether TRPC6 is involved in hypoxia-induced autophagy in cultured human podocytes. Methods: In the present study, an immortalized human podocyte cell line was used. Fluo-3 fluorescence was utilized to determine intracellular Ca2+ concentration ([Ca2+]i), and western blotting was used to measure autophagy and protein expression. Results: We found that blockade TRPC6 by using either TRPC6 siRNA or a TRPC6 blocker attenuated hypoxia-induced autophagy, while enhancement of TRPC6 activity with a TRPC6 activator enhanced hypoxia-induced autophagy. Furthermore, TRPC6-dependent Ca2+ signaling is responsible for hypoxia-induced autophagy since both an intracellular and extracellular Ca2+ chelator abolished hypoxia-induced autophagy. Moreover, we found that blockade of TRPC6 by using either TRPC6 siRNA or a TRPC6 blocker decreased the expression of adenosine monophosphate-activated protein kinase (AMPK), an important signaling molecule in Ca2+-dependent autophagy activation, which is activated under hypoxic conditions. These data suggest that the involvement of TRPC6 in hypoxia-induced autophagy is associated with AMPK signaling. Conclusion: TRPC6 is essential for hypoxia-induced autophagy in podocytes.

scholarly journals Investigation of Cuprizone-Induced Demyelination in mGFAP-Driven Conditional Transient Receptor Potential Ankyrin 1 (TRPA1) Receptor Knockout Mice

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 81 ◽  
Author(s):  
Gábor Kriszta ◽  
Balázs Nemes ◽  
Zoltán Sándor ◽  
Péter Ács ◽  
Sámuel Komoly ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Conditional Knockout ◽  
Genetic Deletion ◽  
The Difference ◽  
Magnetic Resonance Imaging Mri ◽  
Transient Receptor ◽  
And Function ◽  
Knockout Animals

Transient receptor potential ankyrin 1 (TRPA1) receptors are non-selective cation channels responsive to a variety of exogenous irritants and endogenous stimuli including products of oxidative stress. It is mainly expressed by primary sensory neurons; however, expression of TRPA1 by astrocytes and oligodendrocytes has recently been detected in the mouse brain. Genetic deletion of TRPA1 was shown to attenuate cuprizone-induced oligodendrocyte apoptosis and myelin loss in mice. In the present study we aimed at investigating mGFAP-Cre conditional TRPA1 knockout mice in the cuprizone model. These animals were generated by crossbreeding GFAP-Cre+/− and floxed TRPA1 (TRPA1Fl/Fl) mice. Cuprizone was administered for 6 weeks and demyelination was followed by magnetic resonance imaging (MRI). At the end of the treatment, demyelination and glial activation was also investigated by histological methods. The results of the MRI showed that demyelination was milder at weeks 3 and 4 in both homozygous (GFAP-Cre+/− TRPA1Fl/Fl) and heterozygous (GFAP-Cre+/− TRPA1Fl/−) conditional knockout animals compared to Cre−/− control mice. However, by week 6 of the treatment the difference was not detectable by either MRI or histological methods. In conclusion, TRPA1 receptors on astrocytes may transiently contribute to the demyelination induced by cuprizone, however, expression and function of TRPA1 receptors by other cells in the brain (oligodendrocytes, microglia, neurons) warrant further investigation.

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