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Gene & Protein in Disease Sickle cell disease’s journey

Hypoxia,
oxidative stress
Oxy-HbS Deoxy-HbS

Sticky patches on beta-chain of deoxy-HbS

Polymerization of HbS

Sickling of RBCs
Impairment of sheer stress -mediated vasodilatation

Vaso-occlusive crisis Vascular endothelial dysfunction Hemolysis & anemia
Gall stones
Pain Proinflammatory cytokines (pigment stones)

Hemolytic
Inflammatory response
Hypoxia/infarction/ jaundice
necrosis of vital organs Cell-free HbS
Activation of signaling
Acute chest pathways in RBCs
syndrome ↓Arginase ↑ ROS
Stroke
Nephropathy Inactivation of
NO synthesis
Hepatopathy
Cardiopulmonary Cerebro-
Osteonecrosis complications
vascular
Hyposplenism Hypercoagulability diseases
and thromboembolic Pulmonary
complications HTN
Bacterial infections
(Salmonella, S. aureus, Ulcers
Gram-ve enteric bacilli)
Pneumonia
UTI Deep vein thrombosis
Osteomyelitis Pregnancy
Meningitis complications
Septicemia
Figure 1. Pathophysiology in sickle cell disease
Abbreviations: Gram -ve: Gram negative; HTN: Hypertension; RBCs: Red blood cells; ROS: Reactive oxygen species; UTI: Urinary tract infection.
and behavioral and psychosocial factors, are implicated in antioxidant enzyme superoxide dismutase (SOD) and
the disease manifestation and complication. 31 its isoform (SOD2), as well as the variant of the isoform
(SOD2 V16A ), is implicated in mitochondrial function
SCD is marked by increased oxidative stress. This inhibition and vascular dysfunction in SCD. The
33
is resulted primarily from the reduced bioavailability presence of the SOD isoform variant mentioned above
of nitric oxide, as already explained above. Second, is attributed to reduced pulmonary and cardiovascular
the antioxidant defense mechanism consisting of both functions, increased anemia and hemolysis, and
enzymatic and non-enzymatic antioxidants is defective in decreased ability toward physical activities and exercise.
SCD. Third, the presence of cell-free HbS and heme due Cardiopulmonary complications may be attributed to the
to hemolysis is known to increase ROS. 25,32 The resulting fact that chronic anemia decreases the oxygen-carrying
oxidative stress adds to the proinflammatory state and capacity of blood, causing a compensatory increase in
vasculopathy events. The role of the mitochondrial stroke volume and hence cardiac output. This along

Volume 4 Issue 1 (2025) 3 doi: 10.36922/gpd.4361