PMID- 31635212
OWN - NLM
STAT- MEDLINE
DCOM- 20200922
LR  - 20200922
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 9
IP  - 10
DP  - 2019 Oct 18
TI  - Caveolin-1 Regulates P2Y(2) Receptor Signaling during Mechanical Injury in Human 
      1321N1 Astrocytoma.
LID - 10.3390/biom9100622 [doi]
LID - 622
AB  - Caveolae-associated protein caveolin-1 (Cav-1) plays key roles in cellular 
      processes such as mechanosensing, receptor coupling to signaling pathways, cell 
      growth, apoptosis, and cancer. In 1321N1 astrocytoma cells Cav-1 interacts with 
      the P2Y(2) receptor (P2Y(2)R) to modulate its downstream signaling. P2Y(2)R and 
      its signaling machinery also mediate pro-survival actions after mechanical 
      injury. This study determines if Cav-1 knockdown (KD) affects P2Y(2)R signaling 
      and its pro-survival actions in the 1321N1 astrocytoma cells mechanical injury 
      model system. KD of Cav-1 decreased its expression in 1321N1 cells devoid of or 
      expressing hHAP2Y(2)R by ~88% and ~85%, respectively. Cav-1 KD had no significant 
      impact on P2Y(2)R expression. Post-injury densitometric analysis of pERK1/2 and 
      Akt activities in Cav-1-positive 1321N1 cells (devoid of or expressing a 
      hHAP2Y(2)R) revealed a P2Y2R-dependent temporal increase in both kinases. These 
      temporal increases in pERK1/2 and pAkt were significantly decreased in Cav-1 KD 
      1321N1 (devoid of or expressing a hHAP2Y(2)R). Cav-1 KD led to an ~2.0-fold and 
      ~2.4-fold decrease in the magnitude of the hHAP2Y(2)R-mediated pERK1/2 and pAkt 
      kinases' activity, respectively. These early-onset hHAP2Y(2)R-mediated signaling 
      responses in Cav-1-expressing and Cav-1 KD 1321N1 correlated with changes in cell 
      viability (via a resazurin-based method) and apoptosis (via caspase-9 
      expression). In Cav-1-positive 1321N1 cells, expression of hHAP2Y(2)R led to a 
      significant increase in cell viability and decreased apoptotic (caspase-9) 
      activity after mechanical injury. In contrast, hHAP2Y(2)R-elicited changes in 
      viability and apoptotic (caspase-9) activity were decreased after mechanical 
      injury in Cav-1 KD 1321N1 cells expressing hHAP2Y(2)R. These findings support the 
      importance of Cav-1 in modulating P2Y(2)R signaling during mechanical injury and 
      its protective actions in a human astrocytoma cell line, whilst shedding light on 
      potential new venues for brain injury or trauma interventions.
FAU - Martinez, Magdiel
AU  - Martinez M
AD  - Physiology Department, University of Puerto Rico, School of Medicine, San Juan 
      00936-5067, Puerto Rico. magdiel.martinez@upr.edu.
FAU - Martinez, Namyr A
AU  - Martinez NA
AUID- ORCID: 0000-0002-2286-3750
AD  - Physiology Department, University of Puerto Rico, School of Medicine, San Juan 
      00936-5067, Puerto Rico. namyr.martinez@upr.edu.
FAU - Miranda, Jorge D
AU  - Miranda JD
AD  - Physiology Department, University of Puerto Rico, School of Medicine, San Juan 
      00936-5067, Puerto Rico. jorge.miranda3@upr.edu.
FAU - Maldonado, Hector M
AU  - Maldonado HM
AD  - Pharmacology Department, Universidad Central del Caribe, Bayamon 00960-6032, 
      Puerto Rico. hmaldonado1@gmail.com.
FAU - Silva Ortiz, Walter I
AU  - Silva Ortiz WI
AD  - Physiology Department, University of Puerto Rico, School of Medicine, San Juan 
      00936-5067, Puerto Rico. walter.silva@upr.edu.
LA  - eng
GR  - P20 GM103642/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20191018
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (CAV1 protein, human)
RN  - 0 (Caveolin 1)
RN  - 0 (Receptors, Purinergic P2Y2)
RN  - EC 3.4.22.- (CASP9 protein, human)
RN  - EC 3.4.22.- (Caspase 9)
SB  - IM
MH  - Astrocytoma/*metabolism/pathology
MH  - Caspase 9/metabolism
MH  - Caveolin 1/deficiency/isolation & purification/*metabolism
MH  - Cell Survival
MH  - Humans
MH  - Receptors, Purinergic P2Y2/*metabolism
MH  - *Signal Transduction
MH  - *Stress, Mechanical
MH  - Tumor Cells, Cultured
PMC - PMC6843573
OTO - NOTNLM
OT  - P2Y2
OT  - astrocytoma
OT  - brain injury
OT  - caveolae
OT  - caveolin-1
OT  - signaling
COIS- The authors declare that they have no conflicts of interest with the contents of 
      this article.
EDAT- 2019/10/23 06:00
MHDA- 2020/09/23 06:00
PMCR- 2019/10/01
CRDT- 2019/10/23 06:00
PHST- 2019/07/11 00:00 [received]
PHST- 2019/10/01 00:00 [revised]
PHST- 2019/10/02 00:00 [accepted]
PHST- 2019/10/23 06:00 [entrez]
PHST- 2019/10/23 06:00 [pubmed]
PHST- 2020/09/23 06:00 [medline]
PHST- 2019/10/01 00:00 [pmc-release]
AID - biom9100622 [pii]
AID - biomolecules-09-00622 [pii]
AID - 10.3390/biom9100622 [doi]
PST - epublish
SO  - Biomolecules. 2019 Oct 18;9(10):622. doi: 10.3390/biom9100622.