Proapoptotic effects of parathyroid hormone-related protein in type II pneumocytes.
Parathyroid hormone-related protein (PTHrP) promotes or suppresses apoptosis in various settings depending on cell type and context. PTHrP 1-34 and PTHrP 67-86 are type II cell growth factors with effects on pneumocyte growth and surfactant secretion. This study investigated the effects of 24 h pretreatment with these two peptides on rat type II cell apoptosis after 0.3 J/cm2 ultraviolet-B irradiation. Adherent cells decreased in number by 15 +/- 5% and nonadherent cells increased > 5-fold 24 h after ultraviolet irradiation. Cell loss was due predominantly to apoptosis, based on ethidium bromide exclusion, nuclear condensation, and caspase 3 activity. Nuclear condensation increased from 15.6 +/- 2.2% of irradiated cells with no treatment to 25.6 +/- 4.9 and 22.9 +/- 1.8% of cells in ultraviolet/PTHrP 1-34 and ultraviolet/PTHrP 67-86 groups, respectively (P < 0.01), along with a 60% increase in caspase 3 activity. Effects on apoptosis were unaffected by the presence or absence of serum, but were ameliorated by growth to confluence or adherence to fibronectin. PTHrP 1-34 and PTHrP 67-86 augmented inositol phosphate levels, but had minimal effects on cAMP. Thus, PTHrP 1-34 and PTHrP 67-86 sensitize type II cells to apoptosis, possibly by a phospholipase C-dependent mechanism. The effects appear to be regulated by cell-matrix and cell-cell interactions.
Hastings
Randolph H
RH
VA Medical Center (125), 3350 La Jolla Village Dr., San Diego, CA 92161-5085, USA. rhhastings@ucsd.edu
Quintana
Rick A
RA
Sandoval
Rebeca
R
Duey
Devin
D
Rascon
Yvette
Y
Burton
Douglas W
DW
Deftos
Leonard J
LJ
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D020545:Respiratory Mucosa / Q000166:cytology* / Q000378:metabolism* / Q000528:radiation effects; D015290:Second Messenger Systems / Q000502:physiology; D014466:Ultraviolet Rays
D061945:Caspase Inhibitors; D016895:Culture Media, Serum-Free; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D000242:Cyclic AMP; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases