Cardiomyocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 248

physiological stimulus pathological state

(hypertension)

(efforts)

IGF1 ATn2 ET1

HB−EGF

RTK GPCR

EGFR

ADAM12

G

G α q

βγ

−

PI3K α

MAPK

PI3Kγ ERK1/2 p38, JNK

PKB

PKB PKC β PP2B

adaptive hypertrophy maladaptive hypertrophy

Fig. 5.15 Signaling cascades implicated in adaptive and maladaptive hypertrophy. Different
pathways involve different isoforms of phosphoinositide 3-kinase with different effects in the
cardiomyocyte (Source: [ 418 ]).

5.8.2.7 CamK-AMPK Axis

Calcium-activated phosphorylates

(activates) AMPK enzyme. AMP-activated protein kinase switches the cardiomy-
ocyte from ATP consumption (fatty acid, cholesterol, and protein synthesis) to ATP
production from fatty acid and glucose oxidation. 75

calmodulin-dependent kinase kinase- β

5.8.2.8 MAPKs

Activated P38MAPK, JNK, and ERK phosphorylate multiple intracellular
substances such as transcription factors. 76 Signaling launched by ERK1 and ERK2
causes hypertrophy in vivo. Signaling primed by ERK5 is also implicated in cardiac
growth. On the other hand, P38MAPK and JNK provoke cardiomyopathy and hinder
cardiomyocyte hypertrophy. Cardiomyopathy results from the overexpression of
Ras GTPases.

75 AMP-activated protein kinase inhibits acetylCoA carboxylase, 3-hydroxy 3-methyl glutarylCoA
reductase, TOR, and eEF2 kinases. Enzyme AMPK activates mitochondrial ERR

α and PGC1 α .

Fatty acid oxidation is indeed regulated by PPARs and their coactivator PGC1 α . Estrogen-related

receptor ERR α ,ERR β ,andERR γ regulate cardiac energy metabolism. ERR α interacts with

PGC1 .

76 MAP2K1 and MAP2K2 activate ERK1 and ERK2, MAP2K6 and MAP2K3 target P38MAPKs,
and MAP2K4 and MAP2K7 stimulate JNK kinases.

α