TY - CHAP
T1 - Role of ion transport in control of apoptotic cell death
AU - Lang, Florian
AU - Hoffmann, Else Kay
PY - 2012/7
Y1 - 2012/7
N2 - Cell shrinkage is a hallmark and contributes to signaling of apoptosis. Apoptotic cell shrinkage requires ion transport across the cell membrane involving K+ channels, Cl- or anion channels, Na+/H+ exchange, Na+,K+,Cl- cotransport, and Na+/K+ATPase. Activation of K+ channels fosters K+ exit with decrease of cytosolic K+ concentration, activation of anion channels triggers exit of Cl-, organic osmolytes, and HCO3. Cellular loss of K+ and organic osmolytes as well as cytosolic acidification favor apoptosis. Ca2+ entry through Ca2+-permeable cation channels may result in apoptosis by affecting mitochondrial integrity, stimulating proteinases, inducing cell shrinkage due to activation of Ca2+-sensitive K+ channels, and triggering cell-membrane scrambling. Signaling involved in the modification of cell-volume regulatory ion transport during apoptosis include mitogen-activated kinases p38, JNK, ERK1/2, MEKK1, MKK4, the small G proteins Cdc42, and/or Rac and the transcription factor p53. Osmosensing involves integrin receptors, focal adhesion kinases, and tyrosine kinase receptors. Hyperosmotic shock leads to vesicular acidification followed by activation of acid sphingomyelinase, ceramide formation, release of reactive oxygen species, activation of the tyrosine kinase Yes with subsequent stimulation of CD95 trafficking to the cell membrane. Apoptosis is counteracted by mechanisms involved in regulatory volume increase (RVI), by organic osmolytes, by focal adhesion kinase, and by heat-shock proteins. Clearly, our knowledge on the interplay between cell-volume regulatory mechanisms and suicidal cell death is still far from complete and substantial additional experimental effort is needed to elucidate the role of cell-volume regulatory mechanisms in suicidal cell death.
AB - Cell shrinkage is a hallmark and contributes to signaling of apoptosis. Apoptotic cell shrinkage requires ion transport across the cell membrane involving K+ channels, Cl- or anion channels, Na+/H+ exchange, Na+,K+,Cl- cotransport, and Na+/K+ATPase. Activation of K+ channels fosters K+ exit with decrease of cytosolic K+ concentration, activation of anion channels triggers exit of Cl-, organic osmolytes, and HCO3. Cellular loss of K+ and organic osmolytes as well as cytosolic acidification favor apoptosis. Ca2+ entry through Ca2+-permeable cation channels may result in apoptosis by affecting mitochondrial integrity, stimulating proteinases, inducing cell shrinkage due to activation of Ca2+-sensitive K+ channels, and triggering cell-membrane scrambling. Signaling involved in the modification of cell-volume regulatory ion transport during apoptosis include mitogen-activated kinases p38, JNK, ERK1/2, MEKK1, MKK4, the small G proteins Cdc42, and/or Rac and the transcription factor p53. Osmosensing involves integrin receptors, focal adhesion kinases, and tyrosine kinase receptors. Hyperosmotic shock leads to vesicular acidification followed by activation of acid sphingomyelinase, ceramide formation, release of reactive oxygen species, activation of the tyrosine kinase Yes with subsequent stimulation of CD95 trafficking to the cell membrane. Apoptosis is counteracted by mechanisms involved in regulatory volume increase (RVI), by organic osmolytes, by focal adhesion kinase, and by heat-shock proteins. Clearly, our knowledge on the interplay between cell-volume regulatory mechanisms and suicidal cell death is still far from complete and substantial additional experimental effort is needed to elucidate the role of cell-volume regulatory mechanisms in suicidal cell death.
U2 - 10.1002/cphy.c110046
DO - 10.1002/cphy.c110046
M3 - Book chapter
C2 - 23723032
T3 - Comprehensive Physiology
SP - 2037
EP - 2061
BT - Comprehensive physiology
PB - Wiley
ER -
