Blockade of Ryanodine Receptors Stimulates Neurite Outgrowth in Embryos of Spisula solidissima

Jessen-Eller, Kathryn; Steele, Marjorie E; Reinisch, Carol L.; Spitzer, Nicholas C.

doi:10.2307/1542841

Cited by 4 publications

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“…However, there was a slight peak in p120 mRNA levels at 24 hr after fertilization ( Figure 3B), which we have shown to be a critical stage in surf clam development. At this time the serotonergic and dopaminergic systems first appear (17,21) and a ryanodine response develops (20). There is also a primitive neural plexus that coordinates mouth and velum movement, and the shell gland begins producing material for the bivalve shell (17,21).…”

Section: Discussionmentioning

confidence: 99%

“…379 Figure 1. Comparison of deduced amino acid sequence of surf clam p120 (residues 5-588) with molluscan and vertebrate p53 family members from a composite of two multiple alignments (p53 and p53 homologues) using CLUSTAL W 1.7 (20). GenBank accession numbers are in Table 2 standard was gel purified, cloned, and sequenced as described above.…”

Section: Methodsmentioning

confidence: 99%

“…PCBs are lipophilic, environmentally pervasive chemicals that accumulate in plant, animal, and human tissues, promote tumor formation, can damage DNA (14,15), and induce neurotoxic effects during early development in clams (16,17) and humans (18). In vitro fertilization and subsequent developmental studies are easily conducted in the surf clam, Spisula solidissima (16,17,(19)(20)(21), but to our knowledge are not successful in either soft-shell clam or squid. During investigation of these embryos we partially cloned, sequenced, and generated a multiple alignment for a new member of the p53 gene family that codes for an exclusively embryonic 120-kD protein.…”

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confidence: 99%

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A new invertebrate member of the p53 gene family is developmentally expressed and responds to polychlorinated biphenyls.

Jessen-Eller

Kreiling

Begley

et al. 2002

Environ Health Perspect

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The cell-cycle checkpoint protein p53 both directs terminal differentiation and protects embryos from DNA damage. To study invertebrate p53 during early development, we identified three differentially expressed p53 family members (p53, p97, p120) in the surf clam, Spisula solidissima. In these mollusks, p53 and p97 occur in both embryonic and adult tissue, whereas p120 is exclusively embryonic. We sequenced, cloned, and characterized p120 cDNA. The predicted protein, p120, resembles p53 across all evolutionarily conserved regions and contains a C-terminal extension with a sterile alpha motif (SAM) as in p63 and p73. These vertebrate forms of p53 are required for normal inflammatory, epithelial, and neuronal development. Unlike clam p53 and p97, p120 mRNA and protein levels are temporally expressed in embryos, with mRNA levels decreasing with increasing p120 protein (R(2) = 0.97). Highest surf clam p120 mRNA levels coincide with the onset of neuronal growth. In earlier work we have shown that neuronal development is altered by exposure to polychlorinated biphenyls (PCBs), a neurotoxic environmental contaminant. In this study we show that PCBs differentially affect expression of the three surf clam p53 family members. p120 mRNA and protein are reduced the most and earliest in development, p97 protein shows a smaller and later reduction, and p53 protein levels do not change. For the first time we report that unlike p53 and p97, p120 is specifically embryonic and expressed in a time-dependent manner. Furthermore, p120 responds to PCBs by 48 hr when PCB-induced suppression of the serotonergic nervous system occurs.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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A new invertebrate member of the p53 gene family is developmentally expressed and responds to polychlorinated biphenyls.

Jessen-Eller

Kreiling

Begley

et al. 2002

Environ Health Perspect

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“…Ortho-substituted PCBs may activate the ryanodine receptor by interacting with immunophilin, which regulates the ryanodine-sensitive calcium channel gating, leading to release of intracellula r stores of calcium leading to a rise in intracellular calcium concentrations. Blocking the ryanodine receptor leads to increased neurite outgrowth in Spisula embryos (Jessen-Eller et al, 1998). Therefore the ortho-substituted congeners present in the Aroclor 1254 mixture can alter intracellular free calcium levels by either or both of these mechanisms, leading to decreased neurite growth and resulting in the smaller neuronal structures seen in Aroclor 1254-treated embryos.…”

Section: Pcbs Affect Neurodevelopment In Spisula 671mentioning

confidence: 99%

POLYCHLORINATED BIPHENYLS ARE SELECTIVELY NEUROTOXIC IN THE DEVELOPINGSPISULA SOLIDISSIMAEMBRYO

Kreiling

Stephens²,

Kuzirian³

et al. 2000

Journal of Toxicology and Environmental Health, Part A

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Polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants that accumulate to toxic levels in the food chain. Using Spisula solidissima (surf clam) embryos as a developmental model, it was shown that Aroclor 1254 specifically targets two neuronal structures during embryonic development. Embryos were exposed to 1, 10), or 100 ppm Aroclor 1254 or an acetone vehicle control posthatching for 24, 48, and 72 h. Embryos labeled with a serotonin antibody or a neural antigen antibody and a rhodamine-conjugated secondary antibody were viewed by confocal microscopy. The cerebropleural ganglion showed a decrease both in serotonin production and in the size of the serotonin-synthesizing region upon exposure to 10 and 100 ppm Aroclor 1254. These decreases were detectable as early as 48 h postfertilization. When exposed to 100 ppm Aroclor 1254, the primitive neural plexus, which coordinates the movements of the mouth and velum, showed a delay in onset and cessation of expression of a molluscan-specific neural antigen. Exposure to Aroclor 1254 did not affect the overall growth and morphology of the embryos. In addition, analyses of total protein profiles and heat-shock protein 70 levels showed that exposure to Aroclor 1254 did not trigger protein degradation or cause a stress or shock response. These results show that exposure of Spisula embryos to Aroclor 1254 specifically targets neurogenesis while having no effect on the overall growth of the embryo.

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Early development of the serotonergic and dopaminergic nervous system in Spisula solidissima (surf clam) larvae

Kreiling

Jessen-Eller

Miller

et al. 2001

Comparative Biochemistry and Physiology Part A: Molecular &

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Blockade of Ryanodine Receptors Stimulates Neurite Outgrowth in Embryos of Spisula solidissima

Cited by 4 publications

References 0 publications

A new invertebrate member of the p53 gene family is developmentally expressed and responds to polychlorinated biphenyls.

A new invertebrate member of the p53 gene family is developmentally expressed and responds to polychlorinated biphenyls.

POLYCHLORINATED BIPHENYLS ARE SELECTIVELY NEUROTOXIC IN THE DEVELOPINGSPISULA SOLIDISSIMAEMBRYO

Early development of the serotonergic and dopaminergic nervous system in Spisula solidissima (surf clam) larvae

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