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Φυσιολογία 1η διάλεξη
13/11/2009
Κάτια ΚαραλήΕρευνήτρια Β, ΙΙΒΕΑΑ
CELL TISSUE ORGANHeartBrainstomach
SYSTEM
ORGANISM
CARDIOVASCULARNERVOUSGASTROINTESTINAL
CELL COMMUNICATION
physicalelectrical chemical
neurotransmittershormones
Receptor Signaling pathway
Gene transcription
FUNCTION
SERIAL ACTIVATION
COMBINED ACTIVATION and INHIBITION
TRANSCIPTIONAL REGULATIONTRANSLATIONAL REGULATIONPOSTTRANSLATIONAL MODIFICATION
CELL-TO-CELL COMMUNICATION
Modes of signal transduction between different cell types
Types of cellularreceptors
INTERACTION BETWEEN SIGNALING PATHWAYS:
SIMILARITIES TO NEURAL NETWORKS?
A simple neural network. The activity of each neural unit (shown as a circle) is determined by the unit's inputs.The output of each unit is usually a nonlinear function of the unit's inputs. Each connection between units has a particular strength, or "weight," which is indicated by differences in thickness of the connecting arrows.
A simple hypothetical signaling network. The network consists of six receptors and three cytosolic protein kinases. Each receptor activates ( green arrows) or inhibits ( black lines) kinase 1 or 2 or both by an unspecified mechanism. Because signals converge onto kinase 3 (the output kinase), this network will be maximally active only when specificcombinations of extracellular stimuli are present. Although this network is far simpler than any likely to be found in a living cell, it could form part of a more complex signaling pathway.
Schematic representation of cross-talk between signaling pathways
PHYSIOME
The quantitative and integrated description of the Functional behavior of the physiological state of an individual or species.
The physiome describes the physiological dynamics of the normal intact organism
Is built upon information and structure (genome, proteome, morphome).
PHYSIOMEIn its broadest sense,
the physiome should define relationships
from genome to organism and
from functional behavior to gene regulation.
The Physiome Project includes integrated models of components of organisms, such as particular organs or cell systems, biochemical or endocrine systems.
Physiome Project :
Compiles and provides a central repository of databases, linking experimental information and computational models into a single, self-consistent framework.
-----> it aims to promote comprehensive databases and an integrative, analytical approach to the study of medicine.
BODY SYSTEMS
Skeletal and MuscleGastrointestinal (Digestive)Circulatory and RespiratoryUrinaryReproductiveNervousEndocrine
HOMEOSTATIC MEDIATORS
Hormones
Cytokines
Neuro- transmitters
Growth Factors
NUCLEAR RECEPTORS
Early response
Delayed response
THE NUCLEAR RECEPTORS SUPERFAMILY
Glucocorticoid Receptor Signaling
Nucleus
Cell Membrane
HSPs
GREs
Ligand
GR Import
Ligand Binding
Assembly
Export
TF
TFE
Transactivation/Transrepression
mRNA1 mRNA2
Transcriptional Activation by GR through Interaction with Multiple
Protein ComplexesHistone
Acetyltransferases
AF1
AF2
SWI/SNF DRIP/TRAP
p300/CBP
p160 p/CAF
AF1
Transcription initiation complex
Coactivation
Chromatin modulation
RNA polymerase II
Transcription
GREs
GR GR
Non – nuclear receptor families
MODES OF SIGNALING
Typical structure of a G-protein coupled receptor (GPCR)
C. Enzyme-linked receptors
IL-2: an example of a cytokine receptor
Schematic representation of cross-talk between signaling pathways
MOLECULAR MEDIATORS OF ENERGY HOMEOSTASIS
Neuropeptides* Agouti protein* -MSH (-Melanocyte stimulating hormone)* Cocaine- and amphetamine –regulated transcript (Cart)* Hypocretin (or Orexin) 1 and 2* MCH (melanin-concentrating hormone)* NPY (neuropeptide Y)* TRH (thyrotropin-releasing hormone)
Peripheral molecules* Leptin* CCK (cholecystokinin)* Ghrelin* Insulin
Combination of a receptor with the hormone (ligand) leads to activation of adenylate cyclase bound also to themembrane.
Increased activity of adenylate cyclase increases cAMP in the cytosol.cAMP acts inside the cell to alter the rate of process(es).
Endocrine system
Hormones are synthesized by glands
Secreted directly into the blood and carriedto their sites of action
Specifically alter the activities of responsive tissues
HORMONES:
Chemical substances liberated by specific cell types carried by the bloodstream to act on distant target cells.
The cell membrane contains receptors for hormones.
HYPOTHALAMUS
pituitary
PHYSIOLOGICAL ACTIONS
PERIPHERALGLAND
Central Nervous System
Stimuli
Releasing hormone
Trophic hormone
Hormone
GLAND
DEGRADEDDEGRADED
response
prohormone
HORMONE
receptor
effector
DEFECT STIMULATION
Target cell
TISSUEDAMAGE
HYPOFUNCTION HYPERFUNCTION
Destruction block Tumor hyperplasia
Ectopic production
blockstimulation
block
ANTIBODIESANTAGONISTS
ANTIBODIES
Early thoughts: neuronal contributions to various bodily functions could be localized to discrete brain regions or centers.
Experiment (1940s): lesioning of the brainand evaluation of physiology following the distruction of specific areas.-bilateral lesioning of LHA anorexia and weight loss-bilateral lesioning of VMN obesity
In the hypothalamus:
LHA controls hunger
VMN controls satiety
Two classes of neurons involved in responses to leptin in the CNS:
-depolarized-> anorexigenic peptides
-hyperpolarized->orexigenic peptides
Npy increased by starvationnot regulated by overfeeding
Pomc / Cartincreased by starvationdecreased by overfeeding
Leptin : an adipose tissue secreted hormone; the product of the ob gene.
Its main physiological role is to signal nutritional status during periods of food deprivation
Insulin and leptin:
Circulate at levels proportional to body fat contentEnter the CNS in proportion to their plasma levelTheir respective receptors are expressed in neurons involved in energy intakeAdministration of either icv reduces food intakeDeficiency of either or components of their signaling pathway increases food intake
The above strongly support their function as
adiposity signals.
OBESITY
Metabolic rate
Exercise
Food intake
Culture
Monogenic disorders Susceptibility genes
Genes
CardiovascularEndocrineGastrointestinalNervous
