mammalian_toxins
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Transcript mammalian_toxins
Platypus
Short-tailed shrew
Mammalian toxicity: cute but deadly
Ross Brockman
Amanda Mondragon
Monica Moya
Marcelo Moya
Slow loris
Introduction
• Toxins are compounds produced by an organism which
has adverse effects on other organisms.
• Toxins can be produced:
– Defensively
– Offensively
– Both
• Bugs, snakes and fish can be considered toxic but
mammals produce toxins too!
• The platypus, the slow loris and the short-tailed shrew are
some of the few mammals that produce toxins.
Introduction
In class we have talked about venomous spiders, snakes and
other toxic compounds produced by fungi, gacteria and even
plants. We have not discussed venomous mammals, some of
you might not have even be aware that they even existed. Not
many mammalian species produce toxins but the few that do
are fascinating.
We selected this topic to educate our fellow classmates about
their existance, how they produce the toxins and why they
would even want to engage in such a metabolically expensive
process.
In this presentation we will show 3 mammals that produce toxins,
what the toxins do, and the evolutionary significance of
mammal toxicity, among other things.
Platypus
(Ornithorhynchus anatinus)
• A small momotreme, found exclusively on the Eastern
Australian continent and Tasmania.
• Males have small (2-4cm) spurs on hind limbs, which
function both defensive and offensively. (Torres et. al,
2005)
• Defensive against pets, wild dogs, and humans.
• Offensive against other males during breeding season.
Platypus
• The venom:
– A C-type Natriuretic Peptide (OvCNP) is one of the more
prominent and biologically active toxins.
– Similar to those found in some snakes and other mammals.
– Numerous compounds (30+), some called novel peptides,
whos function hasn’t yet been identified. (Torres et. al,
2000)
• OvCNP causes oedema, mast cell histamine release,
swelling of tissue near the site of injection, and
excruciating pain.
Platypus
• OvNGF and some novel proteins have been shown to
have synergistic effects on the pain response felt after
injection (Torres et. al, 2000)
• D-amino acids (identified in bacteria, yeast, and the
skin of some poisonous frogs) may help to stabilize the
venom while it remains stored (Torres et. al, 2005)
Platypus
• Evolutionary implications:
- Females have ankle spurs at birth but they do
not develop or store toxins.
- The location of the toxin may relate to male
aggression against each other.
- Ectopic site for the spur was necessary because
the animal feeds with a bill that is designed for
electrolocation, not injection.
Platypus
• Evolutionary implications:
- The lack of venom producing glands in adult
females implies that they are gender specific for
male-male competition during breeding.
- However, costs are associated with the
production, storage, etc. of glands and toxins that
might also account for their absence in females.
- Further research is needed to identify the
origination, intended function, and overall costs
associated with each of the toxins.
Slow Loris
(Nycticebus coucang)
• Distribution and environment:
– Primarily located in Asian rainforests from India to
Indonesia to Thailand (Wilde, 1972)
– Tree dwelling, nocturnal primates with shy tendencies
Slow Loris
• Morphology (storage of toxins)
– Stored in brachial organ, a glandular area of naked
skin on the flexor surface of arm
– Toxin production seen in offspring as early as 6
weeks
Slow Loris
• Method of venomous injection
– Animal licks elbow prior to biting victim
– Lower jaw has specialized teeth to spread venom
through body
– Bites are painful and often slow healing
– Toxin can also be licked over the body surface of
the young to protect from predators while the
parent is away (Hagey et. al, 2007)
Slow Loris
• Defensive or Offensive? Both?
– Not understood, but most likely only defensive
•Loris prey (i.e. insects) not large enough to require
venom to subdue
•Protection of offspring and habitat likely at the root of
venom production (Krane et. al, 2003)
• Mechanism of action
– Not yet completely understood
– Hypothesized to be similar to cat allergen which
leads to histamine response upon exposure
•70% homology with two chains of Fel d 1 (major allergen
from domestic cat) (Krane et. al, 2003)
Slow Loris
• Physiological response
– Anaphylactic shock following exposure to high
levels of toxin (hypotension, cyanosis of extremities,
microhematuria) (Hagey et. al, 2007)
• Present or future medical uses
– None known
– Researchers still unsure whether toxin is actually
“toxic”, whether it is an acquired allergen or if it is
used as a possible intraspecies communication tool
– Further research required
Short-Tailed Shrew
(Blarina brevicauda)
• Distribution and environment:
• Found in forest and grasslands of eastern half of
united states (Smithsonian).
Short-Tailed Shrew
• Storage of Toxins:
– Submaxillary and the Sublingual glands (Kita et al.
2004)
Short-Tailed Shrew
• Injects venom by biting prey
• Venom delivered by saliva to insect’s
hemolymph through the ruptured exoskeleton
• Can also enter through broken skin
• Typically target the occipital regions of the
mouse’s brain (Martin 1981)
Short-Tailed Shrew
• Defensive or Offensive? Both?
– Typically offensive purpose to capture and
incapacitate prey,
– Also used for defensive purposes.
• Humans experience a local burning sensation
around the bite mark and swelling (Kita et al.
2004).
Short-Tailed Shrew
• Details on use of venom:
– Uses venom to collect a hoard of prey that can be
stored alive
– Prey kept alive sustains nutritional value
– Dead prey eaten first and save the comatose mouse
or immobile insect (Martin 1981)
Short-Tailed Shrew
• Mechanism of the Venom’s action:
• Characterized as a kallikrein protease (Kita et
al. 2004)
• Cleaves kininogen into bradykinin
• Results in vasodilation, inhibited central
nervous system, and edema (Rusiniak and Back
1995)
Short-Tailed Shrew
• Toxicology:
– LD50 for mice injected i.p ≈1 mg/kg. Death within
3 to 5 hours (Kita et al. 2004)
• Physiological response:
– Hypotension, hind limb paralysis, irregular
breathing, and convulsions (Kita et al. 2004)
– The vasodilation contributes to a decrease in blood
pressure (Rusiniak and Back 1995)
Short-Tailed Shrew
• Present or future medical uses:
– Venom has been patented as a paralytic agent for
blocking neuromuscular receptors, an analgesic,
and an insecticide (Stewart et al 2006)
Summary of Mammalian Toxins
Species
Offensive
Action of
Toxin
Defensive
Action of
toxin
Platypus
X
X
Yes, in
Males
Heel
spurs
X
No
Brachial
X
No
Salivary
Slow
Loris
Shorttailed
Shrew
X
Gender
Gland
Specific? Location
Discussion
• Evolutionary pressures have selected for venom
production in a handful of unique mammal
species.
• Only a few of the toxins produced have been
tested and shown to be similar in structure and
function to reptilian forms, but most require
further research to characterize the complicated
protein structures.
Conclusions
Toxin is produced via glands located in different parts of the
animal’s bodies. All three animals produce the toxin mainly
to defend themselves and their offspring.
It is possible that very few mammals are poisonous because
mammals are “smarter” creatures with other means of
obtaining their food.
Mammals also have other ways to avoid predation such as
discussed in the “Evolutionary Arms Race” case in class.
Some squirrels can be immune to a snake’s venom or have
other means of determining the actual threat or even
avoiding it.
Conclusions
Further research is needed to identify the origin, intended
function, and overall metabolic costs associated with each of the
toxins in all three species.
Very little information is available on the slow loris, further
research needs to be done on this fascinating organism.
Slow loris
Short-tailed shrew
Platypus
References
Hagey, L. R., Fry, B. G. and Fitch-Snyder, H. 2007.“Talking Defensively, a Dual Use for the Brachial Gland Exudate of Slow and
Pygmy Lorises.” Developments in Primatology: Progress and Prospects, Primate Anti-Predator Strategies (pp. 253-272).
Springer US: 2007.
Krane, S., Itagaki, Y., Nakanishi, K. and Weldon, P. J. 2003. “Venom” of the slow loris: sequence similarity of prosimian skin gland
protein and Fel d 1 cat allergen. Naturwissenschaften, 90, 60-62.
Kita, M., Nakamura, Y., Okumura, Y., Ohdachi, S.D., Oba, Y., Yoshikuni, M., Kido, H., and Uemura, D. Blarina toxin, a
mammalian lethal venom from the short-tailed shrew Blarina brevicauda: Isolation and Characterization. 2004. Proceedings of
the National Academy of Sciences of the United States of America. Vol. 101. No. 20: 7542-7547.
Martin, I. G. 1981. Venom of the Short-Tailed Shrew (Blarina Brevicauda) as an Insect Immobilizing Agent. Jouranal of
Mammalogy. Vol. 62. No 2: 189-192.
Rusiniak, M., and Back, N. 1995. Kallikrein-Kininogen-Kinin System. Molecular Biology and Biotechnology 1st ed. Berlin, Germany:
Wiley-VCH.
Stewart, J., Steeves, B., and Vernes, K. 2003. Parylitic Peptide for Use in Neuromuscular Therapy. U.S Patent 7485622, filed
November 18, 2003 and issued February 3, 2009.
Smithsonian. North American Animals : Blarina brevicauda. Retrieved on March 30 2009 from
http://www.mnh.si.edu/mna/image_info.cfm?species_id=25
Torres, A. M., de Plater, G., Doverskog, M., Birinyi-Strachan, L.C., Nicholson, G.M., Gallagher, C., and Kuchel, P.W. Defensin-like
Peptide-2 from Platypus Venom: Member of a Class of Peptides with a Distinct Structural Fold. 2000. Biochemistry Journal.
Vol. 348(Pt 3): 649–656.
Torres, A. M., Tsampazi, C., Geraghty, D., Paramjit, S.B., Alewood, P.F. and and Kuchel, P.W. D-Amino Acid Residue in the Ctype Natriuretic Peptide from the Vemon of the Mammal, Ornithorhynchus anatinus, the Australian Platypus. 2005.
Biochemistry Journal. Vol. 15; 391(Pt 2): 215–220.
Wilde, H. 1972. Anaphylactic shock following bite by a ‘slow loris,’ Nycticebus coucang. The American Journal of Tropical
Medicine and Hygiene, 21(5), 592-594.