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Article: TPC Functions in the Immune System.

Steiner, Philip / Arlt, Elisabeth / Boekhoff, Ingrid / Gudermann, Thomas / Zierler, Susanna

2023 Volume 278, Page(s) 71–92

Abstract: Two-pore channels (TPCs) are novel intracellular cation channels, which play a key role in numerous (patho-)physiological and immunological processes. In this chapter, we focus on their function in immune cells and immune reactions. Therefore, we first ... ...

Abstract	Two-pore channels (TPCs) are novel intracellular cation channels, which play a key role in numerous (patho-)physiological and immunological processes. In this chapter, we focus on their function in immune cells and immune reactions. Therefore, we first give an overview of the cellular immune response and the partaking immune cells. Second, we concentrate on ion channels which in the past have been shown to play an important role in the regulation of immune cells. The main focus is then directed to TPCs, which are primarily located in the membranes of acidic organelles, such as lysosomes or endolysosomes but also certain other vesicles. They regulate Ca
MeSH term(s)	Humans ; Calcium Channels/metabolism ; Lysosomes/genetics ; Lysosomes/metabolism ; Immune System/metabolism ; Endosomes/metabolism ; Calcium/metabolism ; Calcium Signaling
Chemical Substances	Calcium Channels ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2023-01-11
Publishing country	Germany
Document type	Journal Article
ISSN	0171-2004
ISSN	0171-2004
DOI	10.1007/164_2022_634
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Article ; Online: Two-Pore Channels Regulate Inter-Organellar Ca

Steiner, Philip / Arlt, Elisabeth / Boekhoff, Ingrid / Gudermann, Thomas / Zierler, Susanna

Cells

2022 Volume 11, Issue 9

Abstract: Two-pore channels (TPCs) are ligand-gated cation-selective ion channels that are preserved in plant and animal cells. In the latter, TPCs are located in membranes of acidic organelles, such as endosomes, lysosomes, and endolysosomes. Here, we focus on ... ...

Abstract	Two-pore channels (TPCs) are ligand-gated cation-selective ion channels that are preserved in plant and animal cells. In the latter, TPCs are located in membranes of acidic organelles, such as endosomes, lysosomes, and endolysosomes. Here, we focus on the function of these unique ion channels in mast cells, which are leukocytes that mature from myeloid hematopoietic stem cells. The cytoplasm of these innate immune cells contains a large number of granules that comprise messenger substances, such as histamine and heparin. Mast cells, along with basophil granulocytes, play an essential role in anaphylaxis and allergic reactions by releasing inflammatory mediators. Signaling in mast cells is mainly regulated via the release of Ca
MeSH term(s)	Anaphylaxis ; Animals ; Calcium/metabolism ; Calcium Channels/genetics ; Endosomes/metabolism ; Histamine ; Homeostasis ; NADP/metabolism
Chemical Substances	Calcium Channels ; NADP (53-59-8) ; Histamine (820484N8I3) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2022-04-26
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11091465
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Article ; Online: Physiological Temperature Changes Fine-Tune

Faro, Dennis / Boekhoff, Ingrid / Gudermann, Thomas / Breit, Andreas

Molecular pharmacology

2021 Volume 100, Issue 3, Page(s) 203–216

Abstract: Norepinephrine (NE) controls many vital body functions by activating adrenergic receptors (ARs). Average core body temperature (CBT) in mice is 37°C. Of note, CBT fluctuates between 36 and 38°C within 24 hours, but little is known about the effects of ... ...

Abstract	Norepinephrine (NE) controls many vital body functions by activating adrenergic receptors (ARs). Average core body temperature (CBT) in mice is 37°C. Of note, CBT fluctuates between 36 and 38°C within 24 hours, but little is known about the effects of CBT changes on the pharmacodynamics of NE. Here, we used Peltier element-controlled incubators and challenged murine hypothalamic mHypoA -2/10 cells with temperature changes of ±1°C. We observed enhanced NE-induced activation of a cAMP-dependent luciferase reporter at 36 compared with 38°C. mRNA analysis and subtype specific antagonists revealed that NE activates
MeSH term(s)	1-Methyl-3-isobutylxanthine/pharmacology ; ARNTL Transcription Factors/metabolism ; Aminopyridines/pharmacology ; Animals ; Cell Line ; Cyclic AMP/metabolism ; Cyclic AMP Response Element-Binding Protein/metabolism ; Cytosol/metabolism ; Forkhead Transcription Factors/metabolism ; GTP-Binding Protein alpha Subunits, Gq-G11/physiology ; GTP-Binding Protein alpha Subunits, Gs/physiology ; Hypothalamus/physiology ; Mice ; Neurons/physiology ; Norepinephrine/pharmacology ; Receptors, Adrenergic, beta-2/biosynthesis ; Receptors, Adrenergic, beta-2/physiology ; Receptors, Adrenergic, beta-3/biosynthesis ; Receptors, Adrenergic, beta-3/physiology ; STAT Transcription Factors/metabolism ; Salmeterol Xinafoate/pharmacology ; Signal Transduction/physiology ; Temperature ; Thyrotropin-Releasing Hormone/genetics ; Thyrotropin-Releasing Hormone/metabolism
Chemical Substances	ARNTL Transcription Factors ; Aminopyridines ; Bmal1 protein, mouse ; BAY 60-6583 ; Creb1 protein, mouse ; Cyclic AMP Response Element-Binding Protein ; Forkhead Transcription Factors ; Receptors, Adrenergic, beta-2 ; Receptors, Adrenergic, beta-3 ; STAT Transcription Factors ; Thyrotropin-Releasing Hormone (5Y5F15120W) ; Salmeterol Xinafoate (6EW8Q962A5) ; Cyclic AMP (E0399OZS9N) ; GTP-Binding Protein alpha Subunits, Gq-G11 (EC 3.6.5.1) ; GTP-Binding Protein alpha Subunits, Gs (EC 3.6.5.1) ; 1-Methyl-3-isobutylxanthine (TBT296U68M) ; Norepinephrine (X4W3ENH1CV)
Language	English
Publishing date	2021-06-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	124034-1
ISSN	1521-0111 ; 0026-895X
ISSN (online)	1521-0111
ISSN	0026-895X
DOI	10.1124/molpharm.121.000309
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Zs.A 525: Show issues

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Article: Differential stimulation of second messenger pathways by distinct classes of odorants.

Boekhoff, I / Breer, H

Neurochemistry international

2009 Volume 17, Issue 4, Page(s) 553–557

Abstract: Using ciliary preparations from rat olfactory epithelia, representative compounds of different odorant classes were assayed for the capability of stimulating the formation of second messengers in a subsecond time range. Fruity, floral and minty odors ... ...

Abstract	Using ciliary preparations from rat olfactory epithelia, representative compounds of different odorant classes were assayed for the capability of stimulating the formation of second messengers in a subsecond time range. Fruity, floral and minty odors were found to induce a transient accumulation of cyclic adenosine monophosphate, whereas the herbaceous and putrid compounds under test caused a rise in inositol trisphosphate concentration.
Language	English
Publishing date	2009-11-16
Publishing country	England
Document type	Journal Article
ZDB-ID	283190-9
ISSN	1872-9754 ; 0197-0186
ISSN (online)	1872-9754
ISSN	0197-0186
DOI	10.1016/0197-0186(90)90043-s
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Article ; Online: Taste Receptors: New Players in Sperm Biology.

Luddi, Alice / Governini, Laura / Wilmskötter, Dorke / Gudermann, Thomas / Boekhoff, Ingrid / Piomboni, Paola

International journal of molecular sciences

2019 Volume 20, Issue 4

Abstract: Taste receptors were first described as sensory receptors located on the tongue, where they are expressed in small clusters of specialized epithelial cells. However, more studies were published in recent years pointing to an expression of these proteins ... ...

Abstract	Taste receptors were first described as sensory receptors located on the tongue, where they are expressed in small clusters of specialized epithelial cells. However, more studies were published in recent years pointing to an expression of these proteins not only in the oral cavity but throughout the body and thus to a physiological role beyond the tongue. The recent observation that taste receptors and components of the coupled taste transduction cascade are also expressed during the different phases of spermatogenesis as well as in mature spermatozoa from mouse to humans and the overlap between the ligand spectrum of taste receptors with compounds in the male and female reproductive organs makes it reasonable to assume that sperm "taste" these different cues in their natural microenvironments. This assumption is assisted by the recent observations of a reproductive phenotype of different mouse lines carrying a targeted deletion of a taste receptor gene as well as the finding of a significant correlation between human male infertility and some polymorphisms in taste receptors genes. In this review, we depict recent findings on the role of taste receptors in male fertility, especially focusing on their possible involvement in mechanisms underlying spermatogenesis and post testicular sperm maturation. We also highlight the impact of genetic deletions of taste receptors, as well as their polymorphisms on male reproduction.
MeSH term(s)	Animals ; Humans ; Male ; Receptors, Cell Surface/metabolism ; Reproduction ; Signal Transduction ; Spermatogenesis ; Spermatozoa/metabolism ; Taste/physiology
Chemical Substances	Receptors, Cell Surface
Language	English
Publishing date	2019-02-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms20040967
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Article ; Online: Inactivation of TRPM7 Kinase Targets AKT Signaling and Cyclooxygenase-2 Expression in Human CML Cells.

Hoeger, Birgit / Nadolni, Wiebke / Hampe, Sarah / Hoelting, Kilian / Fraticelli, Marco / Zaborsky, Nadja / Madlmayr, Anna / Sperrer, Viktoria / Fraticelli, Laura / Addington, Lynda / Steinritz, Dirk / Chubanov, Vladimir / Geisberger, Roland / Greil, Richard / Breit, Andreas / Boekhoff, Ingrid / Gudermann, Thomas / Zierler, Susanna

Function (Oxford, England)

2023 Volume 4, Issue 6, Page(s) zqad053

Abstract: Cyclooxygenase-2 (COX-2) is a key regulator of inflammation. High ... ...

Abstract	Cyclooxygenase-2 (COX-2) is a key regulator of inflammation. High constitutive
MeSH term(s)	Humans ; Proto-Oncogene Proteins c-akt/genetics ; Cyclooxygenase 2/genetics ; TRPM Cation Channels/genetics ; Leukocytes, Mononuclear/metabolism ; Leukemia, Myeloid ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Inflammation ; Protein Serine-Threonine Kinases/genetics
Chemical Substances	Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Cyclooxygenase 2 (EC 1.14.99.1) ; TRPM Cation Channels ; TRPM7 protein, human (EC 2.7.11.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2023-09-15
Publishing country	England
Document type	Journal Article
ISSN	2633-8823
ISSN (online)	2633-8823
DOI	10.1093/function/zqad053
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Article: Role of Chemosensory TRP Channels in Lung Cancer.

Büch, Thomas R H / Büch, Eva A M / Boekhoff, Ingrid / Steinritz, Dirk / Aigner, Achim

Pharmaceuticals (Basel, Switzerland)

2018 Volume 11, Issue 4

Abstract: Transient receptor potential (TRP) channels represent a large family of cation channels and many members of the TRP family have been shown to act as polymodal receptor molecules for irritative or potentially harmful substances. These chemosensory TRP ... ...

Abstract	Transient receptor potential (TRP) channels represent a large family of cation channels and many members of the TRP family have been shown to act as polymodal receptor molecules for irritative or potentially harmful substances. These chemosensory TRP channels have been extensively characterized in primary sensory and neuronal cells. However, in recent years the functional expression of these proteins in non-neuronal cells, e.g., in the epithelial lining of the respiratory tract has been confirmed. Notably, these proteins have also been described in a number of cancer types. As sensor molecules for noxious compounds, chemosensory TRP channels are involved in cell defense mechanisms and influence cell survival following exposure to toxic substances via the modulation of apoptotic signaling. Of note, a number of cytostatic drugs or drug metabolites can activate these TRP channels, which could affect the therapeutic efficacy of these cytostatics. Moreover, toxic inhalational substances with potential involvement in lung carcinogenesis are well established TRP activators. In this review, we present a synopsis of data on the expression of chemosensory TRP channels in lung cancer cells and describe TRP agonists and TRP-dependent signaling pathways with potential relevance to tumor biology. Furthermore, we discuss a possible role of TRP channels in the non-genomic, tumor-promoting effects of inhalational carcinogens such as cigarette smoke.
Language	English
Publishing date	2018-09-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph11040090
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Article ; Online: TRPM7 Kinase Is Essential for Neutrophil Recruitment and Function

Nadolni, Wiebke / Immler, Roland / Hoelting, Kilian / Fraticelli, Marco / Ripphahn, Myriam / Rothmiller, Simone / Matsushita, Masayuki / Boekhoff, Ingrid / Gudermann, Thomas / Sperandio, Markus / Zierler, Susanna

Frontiers in immunology

2021 Volume 11, Page(s) 606893

Abstract: During inflammation, neutrophils are one of the first responding cells of innate immunity, contributing to a fast clearance of infection and return to homeostasis. However, excessive neutrophil infiltration accelerates unsolicited disproportionate ... ...

Abstract	During inflammation, neutrophils are one of the first responding cells of innate immunity, contributing to a fast clearance of infection and return to homeostasis. However, excessive neutrophil infiltration accelerates unsolicited disproportionate inflammation for instance in autoimmune diseases such as rheumatoid arthritis. The
MeSH term(s)	Animals ; Cells, Cultured ; Disease Models, Animal ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neutrophil Infiltration ; Neutrophils/enzymology ; Peritonitis/chemically induced ; Peritonitis/enzymology ; Peritonitis/genetics ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Reactive Oxygen Species/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism ; TRPM Cation Channels/genetics ; TRPM Cation Channels/metabolism ; Tumor Necrosis Factor-alpha
Chemical Substances	Reactive Oxygen Species ; TRPM Cation Channels ; Tumor Necrosis Factor-alpha ; Trpm7 protein, mouse (EC 2.7.1.-) ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; mTOR protein, mouse (EC 2.7.1.1) ; AKT1 protein, human (EC 2.7.11.1) ; Akt1 protein, mouse (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; TRPM7 protein, human (EC 2.7.11.1)
Language	English
Publishing date	2021-02-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.606893
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Article ; Online: Time of day changes in cyclic nucleotides are modified via octopamine and pheromone in antennae of the Madeira cockroach.

Schendzielorz, Thomas / Peters, Wladimir / Boekhoff, Ingrid / Stengl, Monika

Journal of biological rhythms

2012 Volume 27, Issue 5, Page(s) 388–397

Abstract: The cockroach Rhyparobia (Leucophaea) maderae expresses a circadian rhythm in pheromone-dependent mating activity that peaks at the late day/early night. In contrast, the circadian rhythm in olfactory sensitivity of the Madeira cockroach is at its ... ...

Abstract	The cockroach Rhyparobia (Leucophaea) maderae expresses a circadian rhythm in pheromone-dependent mating activity that peaks at the late day/early night. In contrast, the circadian rhythm in olfactory sensitivity of the Madeira cockroach is at its minimum during this time. Until now, the reasons for this obvious discrepancy in phase were not understood. Previously, it was shown that cyclic nucleotides modulate olfactory sensitivity in a zeitgeber time (ZT)-dependent manner. In moths' olfactory receptor neurons, adapting pheromone concentrations elevate cGMP levels, which decrease pheromone sensitivity. In contrast, cAMP elevations sensitized pheromone responses. Thus, with immunoassay kits, it was determined whether cAMP and cGMP baseline levels vary in a ZT-dependent manner in antennal lysates of female R. maderae, revealing underlying circadian rhythms in olfactory sensitivity. Furthermore, it was examined whether adapting pheromone exposure elevates cGMP levels in cockroach antennae, possibly overshadowing underlying circadian rhythms in sensitivity via sensory adaptation. It was shown for the first time that cAMP and cGMP baseline levels oscillate in antiphase in a ZT-dependent manner in an insect's antenna, with the maximum in cAMP concentrations coinciding with maximal mating activity during the late day. Moreover, the cAMP baseline level oscillation expressed a circadian rhythm since it persisted under constant darkness in contrast to cGMP baseline levels. Furthermore, while excess exposure to male pheromones increased cGMP and decreased cAMP baseline levels, the stress hormone octopamine increased adenylyl cyclase activity at all ZTs tested. Therefore, it is suggested that cyclic nucleotide-dependent modulation of olfactory sensitivity due to olfactory overstimulation and stress could be responsible for previously measured phase discrepancies between rhythms in mating behavior and pheromone sensitivity.
MeSH term(s)	Adaptation, Physiological ; Animals ; Arthropod Antennae/physiology ; Circadian Rhythm/physiology ; Cockroaches/physiology ; Cyclic AMP/metabolism ; Cyclic GMP/metabolism ; Female ; Male ; Octopamine/physiology ; Olfactory Receptor Neurons/drug effects ; Olfactory Receptor Neurons/physiology ; Pheromones/physiology ; Sexual Behavior, Animal/drug effects
Chemical Substances	Pheromones ; Octopamine (14O50WS8JD) ; Cyclic AMP (E0399OZS9N) ; Cyclic GMP (H2D2X058MU)
Language	English
Publishing date	2012-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	896387-3
ISSN	1552-4531 ; 0748-7304
ISSN (online)	1552-4531
ISSN	0748-7304
DOI	10.1177/0748730412456265
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Zs.A 2872: Show issues

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Article ; Online: Glucose Enhances Basal or Melanocortin-Induced cAMP-Response Element Activity in Hypothalamic Cells.

Breit, Andreas / Wicht, Kristina / Boekhoff, Ingrid / Glas, Evi / Lauffer, Lisa / Mückter, Harald / Gudermann, Thomas

Molecular endocrinology (Baltimore, Md.)

2016 Volume 30, Issue 7, Page(s) 748–762

Abstract: Melanocyte-stimulating hormone (MSH)-induced activation of the cAMP-response element (CRE) via the CRE-binding protein in hypothalamic cells promotes expression of TRH and thereby restricts food intake and increases energy expenditure. Glucose also ... ...

Abstract	Melanocyte-stimulating hormone (MSH)-induced activation of the cAMP-response element (CRE) via the CRE-binding protein in hypothalamic cells promotes expression of TRH and thereby restricts food intake and increases energy expenditure. Glucose also induces central anorexigenic effects by acting on hypothalamic neurons, but the underlying mechanisms are not completely understood. It has been proposed that glucose activates the CRE-binding protein-regulated transcriptional coactivator 2 (CRTC-2) in hypothalamic neurons by inhibition of AMP-activated protein kinases (AMPKs), but whether glucose directly affects hypothalamic CRE activity has not yet been shown. Hence, we dissected effects of glucose on basal and MSH-induced CRE activation in terms of kinetics, affinity, and desensitization in murine, hypothalamic mHypoA-2/10-CRE cells that stably express a CRE-dependent reporter gene construct. Physiologically relevant increases in extracellular glucose enhanced basal or MSH-induced CRE-dependent gene transcription, whereas prolonged elevated glucose concentrations reduced the sensitivity of mHypoA-2/10-CRE cells towards glucose. Glucose also induced CRCT-2 translocation into the nucleus and the AMPK activator metformin decreased basal and glucose-induced CRE activity, suggesting a role for AMPK/CRTC-2 in glucose-induced CRE activation. Accordingly, small interfering RNA-induced down-regulation of CRTC-2 expression decreased glucose-induced CRE-dependent reporter activation. Of note, glucose also induced expression of TRH, suggesting that glucose might affect the hypothalamic-pituitary-thyroid axis via the regulation of hypothalamic CRE activity. These findings significantly advance our knowledge about the impact of glucose on hypothalamic signaling and suggest that TRH release might account for the central anorexigenic effects of glucose and could represent a new molecular link between hyperglycaemia and thyroid dysfunction.
Language	English
Publishing date	2016-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	639167-9
ISSN	1944-9917 ; 0888-8809
ISSN (online)	1944-9917
ISSN	0888-8809
DOI	10.1210/me.2016-1001
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Zs.A 2261: Show issues

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