Erratum: Errata

Benzaquen, Laura R.; Brugnara, Carlo; Byers, H. Randolph; Gattoni‐Celli, Sebastiano; Halperin, José A.

doi:10.1038/nm0795-717

Cited by 2 publications

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“…Proliferation of normal and DD keratinocytes was sensitive to isotretinoin treatment ( Figure 6F). These results are consistent with previous studies where TRPC1 inhibited translocation of proapoptotic proteins from the ER to mitochondria in neuronal cells (Bollimuntha et al, 2005), and Ca 2ϩ influx inhibitors decreased cell proliferation (Benzaquen et al, 1995) and enhanced apoptosis (Gill et al, 1996;Enfissi et al, 2004). …”

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confidence: 93%

Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca²⁺ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease

Pani

Cornatzer²,

Cornatzer

et al. 2006

MBoC

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The mechanism(s) involved in regulation of store operated calcium entry in Darier's disease (DD) is not known. We investigated the distribution and function of transient receptor potential canonical (TRPC) in epidermal skin cells. DD patients demonstrated up-regulation of TRPC1, but not TRPC3, in the squamous layers. Ca 2؉ influx was significantly higher in keratinocytes obtained from DD patients and showed enhanced proliferation compared with normal keratinocytes. Similar up-regulation of TRPC1 was also detected in epidermal layers of SERCA2 ؉/؊ mice. HaCaT cells expressed TRPC1 in the plasma membrane. Expression of sarco(endo)plasmic reticulum Ca 2؉ ATPase (SERCA)2 small interfering RNA (siRNA) in HaCaT cells increased TRPC1 levels and thapsigargin-stimulated Ca 2؉ influx, which was blocked by store-operated calcium entry inhibitors. Thapsigargin-stimulated intracellular Ca 2؉ release was decreased in DD cells. DD keratinocytes exhibited increased cell survival upon thapsigargin treatment. Alternatively, overexpression of TRPC1 or SERCA2-siRNA in HaCaT cells demonstrated resistance to thapsigargin-induced apoptosis. These effects were dependent on external Ca 2؉ and activation of nuclear factor-B. Isotretinoin reduced Ca 2؉ entry in HaCaT cells and decreased survival of HaCaT and DD keratinocytes. These findings put forward a novel consequence of compromised SERCA2 function in DD wherein up-regulation of TRPC1 augments cell proliferation and restrict apoptosis. We suggest that the anti-apoptotic effect of TRPC1 could potentially contribute to abnormal keratosis in DD. INTRODUCTIONDarier's disease (DD) is an autosomal dominant inherited skin disease, which is characterized by the loss of adhesion between epidermal cells and abnormal keratinization (Burge and Wilkinson 1992). Typical histological findings include focal areas of separation between suprabasal epidermal cells, unusual dyskeratosis with round dyskeratotic keratinocytes (Munro, 1992). Mutations in the sarco(endo)plasmic reticulum Ca 2ϩ ATPase (SERCA) isoform 2b (SERCA2b) gene leads to a loss of function, and these mutations have been shown to cause DD (Sakuntabhai et al., 1999). Most physiological systems are able to compensate for the loss of function of SERCA2b, possibly because of expression of other SERCA isoforms within those tissues (Dhitavat et al., 2003;Tavadia et al., 2004). However, of the multiple isoforms of SERCA1, -2, or -3, only SERCA2b is expressed in keratinocytes (Lytton and MacLennan, 1988;Ruiz-Perez et al., 1999). The mutated SERCA2 fails to sequester cytosolic Ca 2ϩ into the endoplasmic reticulum (ER) lumen, thereby disturbing the otherwise normal Ca 2ϩ homeostasis circuitry within the cells (Zhao et al., 2001;Ahn et al., 2003). Although oral retinoids, such as isotretinoin, have been shown to reduce hyperkeratosis (Burge and Wilkinson, 1992), the mechanism behind dysfunction of SERCA2 resulting in keratosis remains elusive.Ca 2ϩ is an integral signaling element that regulates numerous cellular processes (Clapham, 1995;Berridge e...

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confidence: 93%

Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca²⁺ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease

Pani

Cornatzer²,

Cornatzer

et al. 2006

MBoC

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“…Other well known molecular targets of CLT are intermediate conductance Ca 2ϩ -activated potassium (IK Ca ) channels, including the erythrocyte Gardos channel (KCNN4) (Alvarez et al, 1992); CLT-induced inhibition of the Gardos channel, leading to reduced erythrocyte dehydratation, is a promising therapy in sickle cell disease (Brugnara et al, 1996). In addition, CLT can inhibit cell proliferation in vitro and in vivo, which has been ascribed to a CLT-induced depletion of intracellular Ca 2ϩ stores and blockade of store-dependent Ca 2ϩ influx (Benzaquen et al, 1995). As such, CLT and related substances have potential as antiproliferative and antimetastatic agents for the treatment of various human diseases.…”

Section: Introductionmentioning

confidence: 99%

Transient Receptor Potential Channels in Sensory Neurons Are Targets of the Antimycotic Agent Clotrimazole

Meseguer¹,

Karashima

Talavera

et al. 2008

J. Neurosci.

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Clotrimazole (CLT) is a widely used drug for the topical treatment of yeast infections of skin, vagina, and mouth. Common side effects of topical CLT application include irritation and burning pain of the skin and mucous membranes. Here, we provide evidence that transient receptor potential (TRP) channels in primary sensory neurons underlie these unwanted effects of CLT. We found that clinically relevant CLT concentrations activate heterologously expressed TRPV1 and TRPA1, two TRP channels that act as receptors of irritant chemical and/or thermal stimuli in nociceptive neurons. In line herewith, CLT stimulated a subset of capsaicin-sensitive and mustard oil-sensitive trigeminal neurons, and evoked nocifensive behavior and thermal hypersensitivity with intraplantar injection in mice. Notably, CLTinduced pain behavior was suppressed by the TRPV1-antagonist BCTC [(N-(-4-tertiarybutylphenyl)-4-(3-cholorpyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide)]and absent in TRPV1-deficient mice. In addition, CLT inhibited the cold and menthol receptor TRPM8, and blocked menthol-induced responses in capsaicin-and mustard oil-insensitive trigeminal neurons. The concentration for 50% inhibition (IC 50 ) of inward TRPM8 current was ϳ200 nM, making CLT the most potent known TRPM8 antagonist and a useful tool to discriminate between TRPM8-and TRPA1-mediated responses. Together, our results identify TRP channels in sensory neurons as molecular targets of CLT, and offer means to develop novel CLT preparations with fewer unwanted sensory side effects.

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Erratum: Errata

Cited by 2 publications

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Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca²⁺ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease

Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca²⁺ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease

Transient Receptor Potential Channels in Sensory Neurons Are Targets of the Antimycotic Agent Clotrimazole

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Erratum: Errata

Cited by 2 publications

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Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca2+ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease

Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca2+ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease

Transient Receptor Potential Channels in Sensory Neurons Are Targets of the Antimycotic Agent Clotrimazole

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Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca²⁺ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease

Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca²⁺ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease