Endoplasmic Reticulum

Stress and Pulmonary

Hypertension?

BY PAT BARNES
Endoplasmic Reticulum
Associated Degradation
(ERAD)
2) Recognition
3) Retrotranslocation
4) Ubiquitination
5) Degradation

(Yoshida, 2007)
 Thapsigargin (Tg)
Ø From Plant:
Thapsia garganica
Ø Lower ER [Ca2+]
Ø ER Proteins (ie. BiP)
require Ca2+ for
proper functioning
Ø Raises Cytoplasmic
[Ca2+]

(Yoshida, 2007)
 Thapsigargin (Tg)
 Very Potent Poison
 5nM Tg

(Rutkowskiet al, 2006)

 Cell Culture and
Western Blot
 Cow Fibroblasts
Distal Pulmonary Artery
Cell Lysates
○ Protein Quantification
Western Blot
 α actin

Hypoxia 5nM
Tg
24 12 6 1 12 6 3 1
0
 HRD-1

HRD-
1

(Yamasaki et al, 2005)

 HRD-1

Hypoxia BFA
24 12 6 1 24 12 6 0 - -
 GADD 153/CHOP

Apoptosis
=
CELL DEATH

(Yoshida, 2007)
 GADD 153/CHOP

Hypoxi 5nM Tg
a
24 12 6 1 12 6 3 1
0 2
0
 Rat Model
Comparison
 3276 tc
Endothelin B +/+
Added copy
Monocrotaline

 IHC Staining for P-PERK

KO 7770
 P-PERK
 ER Transmembrane
 Activated by ER Stress
 Translational Attenuation
(Yoshida, 2007)

(Yamasaki et al,
2006)
 3276 tc

200x
40x

400x
 KO 7770

40x
DEATH 200x

4
00x
 Work Cited
 Rutkowski DT, Arnold SM, Miller CN, Wu J, Li J, et al. (2006)
Adaptation to ER stress is mediated by differential stabilities
of pro-survival and pro-apoptotic mRNAs and proteins.
PLoS Biol 4(11): e374. DOI: 10.1371/journal.pbio.0040374
 Yamasaki, Satoshi, Yagishita, Naoko, Tsuchimochi,
Kaneyuki, Nishioka, Kusuki, & Nakajima, Toshihiro (2005).
Rheumatoid arthritis as a hyper-endoplasmic
reticulumassociated. Arthritis Research & Therapy. 7, 181-
186.
 Yoshida, Hiderou (2007).ER stress and diseases. FEBS
Journal. 274, 630–658.