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Oscar Hernández-Hernández

Bio: Oscar Hernández-Hernández is an academic researcher from Necker-Enfants Malades Hospital. The author has contributed to research in topics: Spinocerebellar ataxia & Myotonic dystrophy. The author has an hindex of 13, co-authored 33 publications receiving 388 citations. Previous affiliations of Oscar Hernández-Hernández include CINVESTAV & Instituto Politécnico Nacional.

Papers
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Journal ArticleDOI
11 Feb 2013-Brain
TL;DR: A novel connection between physiological phenotypes and synaptic protein dysregulation, indicative of synaptic dysfunction in myotonic dystrophy type 1 brain pathology is found.
Abstract: Myotonic dystrophy type 1 is a complex multisystemic inherited disorder, which displays multiple debilitating neurological manifestations. Despite recent progress in the understanding of the molecular pathogenesis of myotonic dystrophy type 1 in skeletal muscle and heart, the pathways affected in the central nervous system are largely unknown. To address this question, we studied the only transgenic mouse line expressing CTG trinucleotide repeats in the central nervous system. These mice recreate molecular features of RNA toxicity, such as RNA foci accumulation and missplicing. They exhibit relevant behavioural and cognitive phenotypes, deficits in short-term synaptic plasticity, as well as changes in neurochemical levels. In the search for disease intermediates affected by disease mutation, a global proteomics approach revealed RAB3A upregulation and synapsin I hyperphosphorylation in the central nervous system of transgenic mice, transfected cells and post-mortem brains of patients with myotonic dystrophy type 1. These protein defects were associated with electrophysiological and behavioural deficits in mice and altered spontaneous neurosecretion in cell culture. Taking advantage of a relevant transgenic mouse of a complex human disease, we found a novel connection between physiological phenotypes and synaptic protein dysregulation, indicative of synaptic dysfunction in myotonic dystrophy type 1 brain pathology.

64 citations

Journal ArticleDOI
TL;DR: The results confirm the involvement of PKC in the regulation of H1 receptor‐induced responses and point out to the existence of a feedback mechanism acting via PKC to limit the increase in [Ca2+]i.
Abstract: Glial and glia-derived cells express a variety of receptors for neurotransmitters and hormones, the majority of which evoke both Ca(2+) release from intracellular stores and Ca(2+) entry across the plasma membrane. We investigated the links between histamine H(1) receptor activation, Ca(2+) release from intracellular stores and Ca(2+) influx in human astrocytoma U373 MG cells. Histamine, through a H(1) receptor-mediated effect, evoked an increase in cytoplasmic free calcium concentration ([Ca(2+)](i)) that occurred in two phases: an initial, transient, increase owing to Ca(2+) mobilization from intracellular pools, and a second, sustained increase dependent on both Ca(2+) influx and continuous receptor occupancy. The characteristics of histamine-induced increases in [Ca(2+)](i) were similar to the capacitative entry evoked by emptying of the Ca(2+) stores with thapsigargine, and different from that observed when Ca(2+) influx was activated with OAG (1-oleoyl-2-acetyl-sn-glycerol), a diacylglycerol (DAG) analog. OAG application or increased endogenous DAG, resulting from DAG kinase inhibition, reduced the histamine-induced response. Furthermore, activation of the DAG target, protein kinase C (PKC), by TPA (12-O-tetradecanoyl 4beta-phorbol 13alpha-acetate) resulted in inhibition of the histamine-induced Ca(2+) response, an action prevented by PKC inhibitors. By using reverse transcriptase-polymerase chain reaction analysis, mRNAs for transient receptor potential channels (TRPCs) 1, 4, and 6 as well as for STIM1 (stromal-interacting molecule) and Orai1 were found to be expressed in the U373 MG cells, and confocal microscopy using specific antibodies revealed the presence of the corresponding proteins. Therefore, TRPCs may be candidate proteins forming store-operated channels in the U373 MG cell line. Further, our results confirm the involvement of PKC in the regulation of H(1) receptor-induced responses and point out to the existence of a feedback mechanism acting via PKC to limit the increase in [Ca(2+)](i).

38 citations

Journal ArticleDOI
TL;DR: Two Cys residues are identified involved in the formation of an intermolecular disulfide bond of critical importance for the structure and function of the α(2)δ-1 subunit ofoltage-gated calcium channels.

37 citations

Journal ArticleDOI
TL;DR: Rec recombinant human ZP3 produced in baculovirus-infected Sf9 cells is used to investigate the involvement of Ca(V) channels in the human sperm AR, and overall findings suggest that Ca(v)1 and Ca( V)3 channels participate in human spermAR.

33 citations

Journal ArticleDOI
TL;DR: Genotyping of 300 healthy individuals from Mexican population and compiled data from different ethnicities showed discordant results concerning the hypothesis that SCA disease alleles arise by expansion of large normal alleles.
Abstract: Spinocerebellar ataxias (SCA) are a heterogeneous group of neurodegenerative disorders. CAG (cytosine-adenine-guanine) trinucleotide repeat expansions in the causative genes have been identified as the cause of different SCA. In this study, we simultaneously genotyped SCA1, SCA2, SCA3, SCA6, and SCA7 applying a fluorescent multiplex polymerase chain reaction assay. We analyzed 10 families with SCA (64 patients) from five different communities of Veracruz, a Mexican southeastern state, and identified 55 patients for SCA7 and 9 for SCA2, but none for SCA1, SCA3, or SCA6. To our knowledge, this sample represents one of the largest series of SCA7 cases reported worldwide. Genotyping of 300 healthy individuals from Mexican population and compiled data from different ethnicities showed discordant results concerning the hypothesis that SCA disease alleles arise by expansion of large normal alleles.

29 citations


Cited by
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01 Oct 2014
TL;DR: In this article, the authors used ESC cohesin ChIA-PET data to identify the local chromosomal structures at both active and repressed genes across the genome and reveal that super-enhancer-driven genes generally occur within chromosome structures that are formed by the looping of two interacting CTCF sites co-occupied by co-hesin.
Abstract: The pluripotent state of embryonic stem cells (ESCs) is produced by active transcription of genes that control cell identity and repression of genes encoding lineage-specifying developmental regulators. Here, we use ESC cohesin ChIA-PET data to identify the local chromosomal structures at both active and repressed genes across the genome. The results produce a map of enhancer-promoter interactions and reveal that super-enhancer-driven genes generally occur within chromosome structures that are formed by the looping of two interacting CTCF sites co-occupied by cohesin. These looped structures form insulated neighborhoods whose integrity is important for proper expression of local genes. We also find that repressed genes encoding lineage-specifying developmental regulators occur within insulated neighborhoods. These results provide insights into the relationship between transcriptional control of cell identity genes and control of local chromosome structure.

603 citations

Journal ArticleDOI
TL;DR: The aim of this Review is to examine both the classic and novel roles for these auxiliary subunits in voltage-gated calcium channel function and beyond.
Abstract: The voltage-gated calcium channel α(2)δ and β subunits are traditionally considered to be auxiliary subunits that enhance channel trafficking, increase the expression of functional calcium channels at the plasma membrane and influence the channels' biophysical properties. Accumulating evidence indicates that these subunits may also have roles in the nervous system that are not directly linked to calcium channel function. For example, β subunits may act as transcriptional regulators, and certain α(2)δ subunits may function in synaptogenesis. The aim of this Review is to examine both the classic and novel roles for these auxiliary subunits in voltage-gated calcium channel function and beyond.

325 citations

Journal ArticleDOI
TL;DR: This review critically examines the involvement of Ca(2+) channels in multiple signaling processes needed for spermatozoa to mature, travel towards the egg, and fertilize it.
Abstract: A proper dialogue between spermatozoa and the egg is essential for conception of a new individual in sexually reproducing animals. Ca(2+) is crucial in orchestrating this unique event leading to a new life. No wonder that nature has devised different Ca(2+)-permeable channels and located them at distinct sites in spermatozoa so that they can help fertilize the egg. New tools to study sperm ionic currents, and image intracellular Ca(2+) with better spatial and temporal resolution even in swimming spermatozoa, are revealing how sperm ion channels participate in fertilization. This review critically examines the involvement of Ca(2+) channels in multiple signaling processes needed for spermatozoa to mature, travel towards the egg, and fertilize it. Remarkably, these tiny specialized cells can express exclusive channels like CatSper for Ca(2+) and SLO3 for K(+), which are attractive targets for contraception and for the discovery of novel signaling complexes. Learning more about fertilization is a matter of capital importance; societies face growing pressure to counteract rising male infertility rates, provide safe male gamete-based contraceptives, and preserve biodiversity through improved captive breeding and assisted conception initiatives.

301 citations

Journal ArticleDOI
TL;DR: Well-established in vitro phosphorylation sites of the CaVβ2 subunit of the cardiac L-type CaV1.2 channel were found to be irrelevant for the in vivo regulation of the channel, but the molecular basis of some kinetic properties, such as Ca(2+)-dependent inactivation and facilitation, has been approved by in vivo mutagenesis of the calcium channel gene.
Abstract: The L-type Cav1.2 calcium channel is present throughout the animal kingdom and is essential for some aspects of CNS function, cardiac and smooth muscle contractility, neuroendocrine regulation, and...

283 citations

Journal ArticleDOI
TL;DR: The defensive components of the skin are discussed and the function of skin-resident immune cells in homeostasis and their role in wound healing are focused on.
Abstract: The skin is a complex organ that has devised numerous strategies, such as physical, chemical, and microbiological barriers, to protect the host from external insults. In addition, the skin contains an intricate network of immune cells resident to the tissue, crucial for host defense as well as tissue homeostasis. In the event of an insult, the skin-resident immune cells are crucial not only for prevention of infection but also for tissue reconstruction. Deregulation of immune responses often leads to impaired healing and poor tissue restoration and function. In this review, we will discuss the defensive components of the skin and focus on the function of skin-resident immune cells in homeostasis and their role in wound healing.

274 citations