PMID- 18241324
OWN - NLM
STAT- MEDLINE
DCOM- 20080328
LR  - 20091119
IS  - 1474-9726 (Electronic)
IS  - 1474-9718 (Linking)
VI  - 7
IP  - 2
DP  - 2008 Mar
TI  - Evidence that age-related changes in p38 MAP kinase contribute to the decreased 
      steroid production by the adrenocortical cells from old rats.
PG  - 168-78
LID - 10.1111/j.1474-9726.2007.00364.x [doi]
AB  - The current studies were initiated to investigate whether excessive oxidative 
      stress exerts its antisteroidogenic action through modulation of 
      oxidant-sensitive mitogen-activated protein kinase (MAPK) signaling pathways. 
      Western blot analysis indicated that aging caused increased phosphorylation and 
      activation of rat adrenal p38 MAPK, but not the ERK1/2 or JNK1/2. Lipid 
      peroxidation measurements (an index of cellular oxidative stress) indicated that 
      adrenal membranes from young animals contained only minimal levels of endogenous 
      thiobarbituric acid-reactive substances (TBARS), and exposure of membranes to 
      enzymatic and non-enzymatic pro-oxidants enhanced TBARS formation approximately 
      12- and 20-fold, respectively. The adrenal membranes from old animals showed much 
      more susceptibility to lipid peroxidation and exhibited roughly 4- to 6-fold 
      higher TBARS formation than young controls both under basal conditions and in 
      response to pro-oxidants. Qualitatively similar results were obtained when lipid 
      peroxide formation was measured using a sensitive FOXRS (ferrous 
      oxidation-xylenol orange-reactive substances) technique. We next tested whether 
      aging-induced excessive oxidative insult alters steroidogenesis through 
      modulation of MAPK signaling pathway. Treatment of adrenocortical cells from old 
      rats with specific p38 MAPK inhibitors restored Bt(2)cAMP-stimulated 
      steroidogenesis approximately 60-70% of the value seen in cells of young animals. 
      Likewise, pretreatment of cells with reactive oxygen species (ROS) scavengers 
      MnTMPyP and N-acetyl cysteine also partially rescued age-induced loss of steroid 
      production. In contrast, simultaneous treatment of cells with ROS scavengers and 
      p38 MAPK inhibitor did not produce any additional effect suggesting that both 
      types of inhibitors exert their stimulatory action through inhibition of p38 MAPK 
      activation. Collectively, these results indicate that p38 MAPK functions as a 
      signaling effector in oxidative stress-induced inhibition of steroidogenesis 
      during aging.
FAU - Abidi, Parveen
AU  - Abidi P
AD  - Geriatric Research, Education and Clinical Center, Department of Veterans Affairs 
      Palo Alto Health Care System, Palo Alto, CA 94304, USA.
FAU - Leers-Sucheta, Susan
AU  - Leers-Sucheta S
FAU - Cortez, Yuan
AU  - Cortez Y
FAU - Han, Jiahuai
AU  - Han J
FAU - Azhar, Salman
AU  - Azhar S
LA  - eng
GR  - DK56339/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20080128
PL  - England
TA  - Aging Cell
JT  - Aging cell
JID - 101130839
RN  - 0 (Adrenal Cortex Hormones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Metalloporphyrins)
RN  - 0 (Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin)
RN  - 0 (Oxidants)
RN  - 0 (Thiobarbituric Acid Reactive Substances)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Adrenal Cortex/enzymology
MH  - Adrenal Cortex Hormones/biosynthesis/*deficiency
MH  - Age Factors
MH  - Aging/*metabolism
MH  - Animals
MH  - Enzyme Activation
MH  - Enzyme Inhibitors
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Free Radical Scavengers
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Lipid Peroxidation
MH  - MAP Kinase Signaling System
MH  - Male
MH  - Metalloporphyrins
MH  - Oxidants
MH  - Oxidative Stress/*physiology
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Thiobarbituric Acid Reactive Substances/analysis
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
EDAT- 2008/02/05 09:00
MHDA- 2008/03/29 09:00
CRDT- 2008/02/05 09:00
PHST- 2008/02/05 09:00 [pubmed]
PHST- 2008/03/29 09:00 [medline]
PHST- 2008/02/05 09:00 [entrez]
AID - ACE364 [pii]
AID - 10.1111/j.1474-9726.2007.00364.x [doi]
PST - ppublish
SO  - Aging Cell. 2008 Mar;7(2):168-78. doi: 10.1111/j.1474-9726.2007.00364.x. Epub 
      2008 Jan 28.